Gene cluster of vicenistatin biosynthesis, a vicenisamine glycosyltransferase polypeptide, and a gene encoding the polypeptide

ABSTRACT

To achieve enzymatic production of vicenistatin, a valuable compound, this invention provides enzymes involved in biosynthesis of vicenistatin and genes encoding the enzymes. This invention provides base sequence of the vin cluster which encodes enzyme complex responsible for biosynthesis of vicenistatin. This invention further provides a glycosyltransferase (VinC enzyme), which catalyzes production of vicenistatin using dTDP-vicenisamine as a substrate. Moreover, this invention provides a gene (vinC gene) encoding the enzyme. The VinC enzyme is useful for enzymatic synthesis of valuable compound vicenistatin. Furthermore, it is suggested that use of the VinC enzyme will enable development of novel polyketide glycosides.

BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] This invention relates to an enzyme cluster of vicenistatin biosynthesis enzyme, and a gene cluster of vicenistatin biosynthesis enzyme encoding the enzyme cluster. Particularly, this invention relates to VinC enzyme, which is a glycosyltransferase catalyzing the reaction to produce vicenistatin using dTDP-vicenisamine as a substrate, and to vinC gene encoding the enzyme.

[0003] 2. Prior Art

[0004] Enthusiastic investigation on genes encoding biosynthesis of polyketide compounds has been performed worldwide, and attempts to create new polyketides have been also performed by deletion or insertion of the gene. Under such situation, to obtain novel polyketide compounds, not only simple polyketides but also complex polyketides have attracted attention of researches as novel genetic resources, and wide-range investigation has been performed.

[0005] Vicenistatin is an anticancer antibiotic produced by Streptomyces sp. HC-34 strain of actinomycetes. From a study on experimental human cancer research using nude mice which received transplantation of human cancer cells, it has been known that vicenistatin can markedly inhibit growth of human intestinal cancer cells. As to its chemical structure, plane structure of vicenistatin and absolute conformation on vicenisamine (sugar moiety of vicenistatin) were firstly elucidated. Then, the absolute configuration of the aglycon was determined. The actinomycetes species capable of producing vicenistatin was identified as Streptomyces halstedii HC-34.

[0006] As to the biosynthetic pathway of vicenistatin, it was elucidated that it consists of the following steps. Firstly, glutamate as a starting material undergoes a series of reactions including mutase reaction to produce a polyketide starter unit. Then, propionate and acetate are introduced as precursors to evoke a normal polyketide elongation reaction to produce a characteristic 20-membered cyclic aglycon portion. It was clarified that vicenisamine was derived from glucose via conversion of functional groups similar to reaction involved in production of other aminosugars, and N-methyl groups derived from methionine was incorporated for biosynthesis of vicenisamine.

[0007] To create a novel compound by further modification on the molecular structure through biosynthetic engineering, attempts have been made for identification of genes responsible for biosynthesis of vicenistatin. A number of novel lactam polyketide antibiotics were discovered by researches mainly achieved in Japan, and some studies were reported on biosynthetic precursors. However, no study has been made on the genes and enzymes involved in the biosynthesis of those compounds.

SUMMARY OF THE INVENTION

[0008] Vicenistatin has a structure comprising unique 20-membered lactam glycoside and it is a noteworthy anti biotic because of its strong inhibitory effect on growth of human solid cancer cells transplanted into experimental models. However, vicenistatin is not put into practical use yet because of its limited solubility and moderate toxicity. However, if these disadvantages will be conquered in the future by researches on chemical or biosynthetic engineering, it will provide a useful medicine. Therefore, for the purpose to achieve development of novel useful substances by biosynthetic engineering, elucidation and modification on the system involved in biosynthesis of the unique chemical structure are required. Thus, the object of this invention is to obtain genes involved in biosynthesis of vicenistatin, which is the principle genes in the biosynthetic system, and to elucidate functions of the genes.

[0009] Vicenistatin is a glycoside containing an aminosugar. There is no known compound containing sugar moiety identical to vicenisamine, but it was assumed that some similar genes responsible for biosynthesis of similar aminosugars might be involved in biosynthesis of vicenistatin. It is known that the aglycon portion is a polyketide derived from acetate/propionate as its precursor. From this knowledge, it was predicted that genes similar to those responsible for biosynthesis of polyketide synthases (PKS) were involved in biosynthesis of the aglycon portion. However, it was also known that the polyketide starter unit comprises unique amino acids derived from glutamate, therefore, it was predicted that certain novel genes different from those conventionally known might be involved in biosynthesis of this polyketides.

[0010] In this invention, an attempt was made to identify genes responsible for biosynthesis of vicenistatin, using knowledge on ketosynthases (KS), which is indispensable for biosynthesis of polyketides and having high homology with synthases of various polyketides, as well as analogies of aminosugars and singular starter unit, using techniques of PCR and hybridization. As a result, the genes encoding cluster of enzymes indispensable to produce the ultimate structure of vicenistatin were identified and base sequences of the genes were sequenced. This knowledge provides a great possibility for modification of vicenistatin biosynthesis through biosynthetic engineering, by methods such as modification, deletion or duplication in the base sequence of the biosynthetic genes, or insertion of some exogenous genes, etc.

[0011] The first aspect of this invention is to provide a gene cluster comprising a base sequence represented by base Nos. 1-64492 shown in the SEQ ID No. 1 in the sequence listing.

[0012] The second aspect of this invention is to provide a polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-419 shown in the SEQ ID No. 4 in the sequence listing. A polypeptide comprising an amino acid sequence in which a part of the amino acid sequence is deleted or another amino acid sequence is added to the amino acid sequence, or a part of the amino acid sequence is substituted with another amino acid sequence, and exhibiting enzymatic activity as a glycosyltransferase, is also included within the scope of this invention. Furthermore, a gene encoding the polypeptide is also included within the scope of this invention.

[0013] The third aspect of this invention is to provide a gene comprising a base sequence represented by base Nos. 2790-4049 shown in the SEQ ID No. 1 in the sequence listing. A gene comprising a base sequence in which a part of the base sequence is deleted or another base sequence is added to the base sequence, or a part of the base sequence is substituted with another base sequence, and encoding a polypeptide exhibiting enzymatic activity as a glycosyltransferase, is also included within the scope of this invention.

[0014] The fourth aspect of this invention is to provide a method for production of vicenistatin by catalytic reaction of the glycosyltransferase comprising the polypeptide as described above, using dTDP-vicenisamine as a starting material.

BRIEF DESCRIPTION OF THE DRAWINGS

[0015]FIG. 1 is a schematic figure showing gene mapping of the gene obtained in this study.

[0016]FIG. 2 is a figure showing results of homology analysis performed on the respective open reading frames (ORFs).

[0017]FIG. 3 is a figure showing the biosynthetic pathway of vicenistatin agylcon.

[0018]FIG. 4 is a figure showing the biosynthetic pathway of vicenistatin.

[0019]FIG. 5 is a figure showing the synthetic pathway of the substrates (dTDP-vicenisamine, dTDP-mycarose, and dTDP-2-deoxyglucose) used for the enzyme reaction.

DETAILED DESCRIPTION OF THE INVENTION

[0020] A cosmid library comprising DNA insert fragments of about 40 kbp were constructed according to the conventional method, from the genome of Streptomyces halstedii sp. HC-34, which is a vecenistatin (an antibiotic) producing bacteria. From knowledge on biosynthesis of aminosugar, it was assumed that both of dTDP-glucose-4,6-dehydratase and dTDP-4-keto-6-deoxyglucose-2,3-dehydratase were involved in biosynthesis of vicenisamine, which is a sugar component of vecenistatin. Therefore, the known base sequences of the enzymes were used to design probes and investigations were performed using PCR and other approaches. Consequently, two kinds of cosmids were isolated.

[0021] Subsequently, the two kinds of cosmids were sequenced. In general, genes involved in biosynthesis of antibiotics form a cluster and exist in forms of one mass. In view of this knowledge, the inventors searched for which is the gene encoding the enzyme concerned here. In this case, the previously reported knowledge on the mechanism of biosynthesis of antibiotics was effective. Particularly, in view of the knowledge on the sequence conserved among genes encoding ketosynthase (KS) involved in polyketide biosynthesis, the inventors limited candidate genes responsible for vicenistatin biosynthesis enzyme to cosmids K1B10 and K1D11. They analyzed on base sequence of the genes existing adjacent to these cosmids, and functions of respective open reading frames (ORFs) were predicted from homology search from existing databases.

[0022] Again, the previous observation was-effective, that is, it was known that the starter unit of the lactam portion of vicenistatin was derived from glutamate and the starter unit was formed via a mutase reaction. Based on this knowledge, the inventors found ORFs having high homology with known glutamate mutase. Moreover, they confirmed that putative function of respective modules in the ORFs highly correlated with the biosynthetic pathway of vicenistatin. The entire cluster and the respective open reading frames of the sugar portion and the lactam portion were named to be vin gene, in connection with the name of vicenistatin.

[0023] Furthermore, to confirm the function of the vin gene cluster, the inventors expressed glycosyltransferase gene (vinC) in E. coli, and the glycosyltransferase was used for the reaction between chemically synthesized dTDP-vicenisamine and the aglycon chemically derived from vicenistatin. As a result, it was confirmed that this vinC efficiently catalyzed this reaction as a transferase. Therefore, it was confirmed that the vin gene cluster was responsible for vicenistatin biosynthesis. Hitherto, the gene identified to be a biosynthetic gene of macrocyclic lactam antibiotic was limited to only rifamycin, which is a member of ansamycin group antibiotics. Rifamycin is different from vicenistatin in various aspects including its chemical structure and biological activity, therefore, the gene cluster of this invention will serve as a valuable resource for further creation of novel substances, using techniques of biosynthetic engineering.

[0024] As to vinC gene which function was identified in this invention, the VinC protein was produced in a large scale in E. coli, by the technique of electrophoresis. In addition, to confirm its function, glycosyltransferase reaction was performed between chemically synthesized dTDP-vicenisamine and the vicenistatin aglycon. Moreover, it was detected that the VinC enzyme can catalyze transferase reaction of chemically synthesized dTDP-mycarose or dTDP-2-deoxyglucose with the vicenistatin aglycon. From this result, it was suggested that use of the enzyme of this invention would enable synthesis of a novel polyketide glycosides hitherto unknown. According to this invention, genes responsible for biosynthesis of vicenistatin (an anticancer antibiotic) were identified. Among these enzymes, particularly, the function of VinC was confirmed as a glycosyltransferase.

[0025] The base sequence described in SEQ ID No.1 in the sequence listing represents the gene corresponding to the entire region of the gene cluster of vicenistatin biosynthesis enzyme, obtained by analysis of the base sequence of the region of cosmid K1B10 and the regions adjacent to it. Genes involved in biosynthesis of vicenistatin form a cluster and the genes described in SEQ ID No.1 in the sequence listing encode various enzymes involved in vicenistatin biosynthesis, not only the glycosyltransferase.

[0026] That is, in the gene described in SEQ ID No.1 in the sequence listing, the portion corresponding to base Nos. 2790-4049 encodes a glycosyltransferase, serving for biosynthesis of vicenistatin using vicenisamine as a substrate. The transferase of vicenisamine is a polypeptide represented by an amino acid sequence as listed in the SEQ ID No.4 in the sequence listing.

[0027] The polypeptide consisting of an amino acid sequence in which a part of said polypeptide represented by amino acid sequence shown in SEQ ID NO: 4 in the sequence listing is deleted, substituted or added with another amino acid sequence means a polypeptide in which ten or less, preferably five or less, and more preferably two or less amino acids of the sequence is deleted, substituted or added to the amino acid sequence represented by SEQ ID NO: 4 in the sequence listing. Moreover, such polypeptide exhibits homology 90% or more, preferably 95% or more and still preferably 99% or more with the amino acid sequence represented by in SEQ ID NO: 4 in the sequence listing. Such polypeptide is also within the scope of this invention so far as it exhibits enzymatic activity as a glycosyltransferase, that is, catalyzing synthesis of vicenistatin using vicenisamine as a substrate.

[0028] According to technique of gene recombination, artificial modification can be achieved at a specific site of basic DNA, without alteration or with improvement of basic characteristic of said DNA. Concerning a gene having native sequence provided according to this invention or modified sequence different from said native sequence, it is also possible to perform artificial modification such as insertion, deletion or substitution to obtain gene of equivalent or improved characteristic compared with said native gene. Moreover, a gene with such mutation is also included in the scope of this invention.

[0029] That is, the gene, consisting of a base sequence in which a part of said gene represented by base Nos. 2790-4049 in the SEQ ID No.1 in the sequence listing is deleted, substituted or added with another base sequence means a gene in which ten or less, preferably five or less, and more preferably two or less bases of the sequence is deleted, substituted or added to the base sequence base Nos. 2790-4049 shown in the SEQ ID No.1 in the sequence listing. Moreover, such gene exhibits homology 90% or more, preferably 95% or more and still preferably 99% or more with the base sequence represented by base Nos. 2790-4049 shown in the SEQ ID No. 1 in the sequence listing. Such gene is also within the scope of this invention so far as it encodes a polypeptide exhibiting enzymatic activity as a glycosyltransferase, that is, catalyzing synthesis of vicenistatin using vicenisamine as a substrate. In addition, such gene hybridizes with the base sequence represented by base Nos. 2790-4049 shown in the SEQ ID No.1 in the sequence listing under stringent conditions.

[0030] The condition for hybridization can be selected by those skilled in the art ad libitum. That is, hybridization can be performed by the following procedure. DNA molecules or RNA molecules to be tested are transferred onto a membrane, then the membrane is hybridized with a labeled probe in a proper hybridization buffer. The hybridization buffer may comprise, for example, 5×SSC, 5% (weight %) dextran sulfate, {fraction (1/20)} volume of blocking reagent and 2 to 7×SSC, however, other various formulation can be also used for the hybridization buffer. The blocking reagent for nucleic acid hybridization may comprise, for example, a buffer (pH 7.5) containing 0.1M maleic acid and 0.15M sodium chloride, and commercially available blocking reagent for hybridization may be dissolved into the buffer at the concentration of 10%. The 20×SSC solution may comprise 3M sodium chloride and 0.3M citrate, and the SSC solution may be preferably utilized at the concentration of 3 to 6×SSC, more preferably at the concentration of 4 to 5×SSC.

[0031] The temperature for hybridization may preferably be 40 to 80° C., more preferably be 50 to 70° C., further more preferably be 55 to 65° C. Incubation may be performed from several hours to overnight, then washed by a washing buffer. The temperature for washing may preferably be room temperature, more preferably it may be the temperature used for hybridization. The formulation for the washing buffer may preferably comprise 6×SSC and 0.1% (weight %) SDS, more preferably may comprise 4×SSC and 0.1% (weight %) SDS, further preferably may comprise 2×SSC and 0.1% (weight %) SDS, more further preferably may comprise 1×SSC and 0.1% (weight %) SDS, most preferably may comprise 0.1×SSC and 0.1% (weight %) SDS. The membrane may be washed by such washing buffer, then DNA molecule or RNA molecule may be distinguished by the hybridization with the labeled probe.

[0032] It is known that the gene cluster shown in the sequence ID No. 1 of the sequence listing includes plural ORFs, except for that of the glycosyltransferase, and predicted amino acid sequences encoded by the ORFs are also obtained. Moreover, the functions of the enzymes defined by these amino acid sequences can be predicted based on the results of homology search with amino acid sequences derived from various enzymes.

[0033] In the SEQ ID No. 1 in the sequence listing, bases Nos. 695-1762 represents an ORF and the gene corresponding to the ORF (vinA) encodes a protein consisting of 355 amino acids. The sequence shown in SEQ ID No. 2 in the sequence listing represents predicted amino acid sequence encoded by the vinA gene. As will be detailed later, that protein is assumed to be dTDP-glucose synthase.

[0034] In the SEQ ID No. 1 in the sequence listing, bases Nos. 1759-2730 represents an ORF and the gene corresponding to the ORF (vinB) encodes a protein consisting of 323 amino acids. The sequence shown in SEQ ID No. 3 in the sequence listing represents predicted amino acid sequence encoded by the vinB gene. As will be detailed later, that protein is assumed to be dTDP-glucose 4,6-dehydratase.

[0035] In the SEQ ID No. 1 in the sequence listing, bases Nos. 4412-11194 represents an ORF and the gene corresponding to the ORF (vinP2) encodes a protein consisting of 2260 amino acids. The sequence shown in SEQ ID No. 5 in the sequence listing represents predicted amino acid sequence encoded by the vinP2 gene. As will be detailed later, that protein is assumed to be polyketide synthase module.

[0036] In the SEQ ID No. 1 in the sequence listing, bases Nos. 11260-21348 represents an ORF and the gene corresponding to the ORF (vinP3) encodes a protein consisting of 3362 amino acids. The sequence shown in SEQ ID No. 6 in the sequence listing represents predicted amino acid sequence encoded by the vinP3 gene. As will be detailed later, that protein is assumed to be polyketide synthase module.

[0037] In the SEQ ID No. 1 in the sequence listing, bases Nos. 21411-32837 represents an ORF and the gene corresponding to the ORF (vinP4) encodes a protein consisting of 3808 amino acids. The sequence shown in SEQ ID No. 7 in the sequence listing represents predicted amino acid sequence encoded by the vinP4 gene. As will be detailed later, that protein is assumed to be polyketide synthase module.

[0038] In the SEQ ID No. 1 in the sequence listing, bases Nos. 33262-33972 (complementary strand) represents an ORF and the gene corresponding to the ORF (vinG) encodes a protein consisting of 236 amino acids. The sequence shown in SEQ ID No. 8 in the sequence listing represents predicted amino acid sequence encoded by the vinG gene. As will be detailed later, that protein is assumed to be N-methyltransferase, that is, an enzyme closely related to dTDP-N-dimethyldesosamine-N-methyltransferase.

[0039] In the SEQ ID No. 1 in the sequence listing, bases Nos. 33980-35173 (complementary strand) represents an ORF and the gene corresponding to the ORF (vinF) encodes a protein consisting of 397 amino acids. The sequence shown in SEQ ID No. 9 in the sequence listing represents predicted amino acid sequence encoded by the vinF gene. As will be detailed later, that protein is assumed to be dTDP-hexose-aminotransferase.

[0040] In the SEQ ID No. 1 in the sequence listing, bases Nos. 35320-36801 represents an ORF and the gene corresponding to the ORF (vinD) encodes a protein consisting of 493 amino acids. The sequence shown in SEQ ID No. 10 in the sequence listing represents predicted amino acid sequence encoded by the vinD gene. As will be detailed later, that protein is assumed to be dTDP-4-keto-6-deoxyglucose-2,3-dehydratase.

[0041] In the SEQ ID No. 1 in the sequence listing, bases Nos. 36849-37841 represents an ORF and the gene corresponding to the ORF (vinE) encodes a protein consisting of 330 amino acids. The sequence shown in SEQ ID No. 11 in the sequence listing represents predicted amino acid sequence encoded by the vinE gene. As will be detailed later, that protein is assumed to be dTDP-4-keto-6-deoxyhexose-2,3-reductase.

[0042] In the SEQ ID No. 1 in the sequence listing, bases Nos. 38022-38498 represents an ORF and the gene corresponding to the ORF (vinH) encodes a protein consisting of 158 amino acids. The sequence shown in SEQ ID No. 12 in the sequence listing represents predicted amino acid sequence encoded by the vinH gene. As will be detailed later, that protein is assumed to be S-subunit of glutamate mutase.

[0043] In the SEQ ID No. 1 in the sequence listing, bases Nos. 38495-39904 represents an ORF and the gene corresponding to the ORF (vinI) encodes a protein consisting of 469 amino acids. The sequence shown in SEQ ID No. 13 in the sequence listing represents predicted amino acid sequence encoded by the vinI gene. As will be detailed later, that protein is assumed to be E-subunit of glutamate mutase.

[0044] In the SEQ ID No. 1 in the sequence listing, bases Nos. 39990-40889 represents an ORF and the gene corresponding to the ORF (vinJ) encodes a protein consisting of 299 amino acids. The sequence shown in SEQ ID No. 14 in the sequence listing represents predicted amino acid sequence encoded by the vinJ gene. As will be detailed later, that protein is assumed to be proline iminopeptidase.

[0045] In the SEQ ID No. 1 in the sequence listing, bases Nos. 40886-41869 represents an ORF and the gene corresponding to the ORF (vinK) encodes a protein consisting of 327 amino acids. The sequence shown in SEQ ID No. 15 in the sequence listing represents predicted amino acid sequence encoded by the vinK gene. As will be detailed later, that protein is assumed to be acyl CoA-ACP transacylase closely related to malonyl CoA-ACP transacylase.

[0046] In the SEQ ID No. 1 in the sequence listing, bases Nos. 41987-42235 represents an ORF and the gene corresponding to the ORF (vinL) encodes a protein consisting of 82 amino acids. The sequence shown in SEQ ID No. 16 in the sequence listing represents predicted amino acid sequence encoded by the vinL gene. As will be detailed later, that protein is assumed to be acyl carrier protein.

[0047] In the SEQ ID No. 1 in the sequence listing, bases Nos. 42289-43863 represents an ORF and the gene corresponding to the ORF (vinM) encodes a protein consisting of 524 amino acids. The sequence shown in SEQ ID No. 17 in the sequence listing represents predicted amino acid sequence encoded by the vinM gene. As will be detailed later, that protein is assumed to be non-ribosomal type peptide synthase.

[0048] In the SEQ ID No. 1 in the sequence listing, bases Nos. 44156-45592 represents an ORF and the gene corresponding to the ORF (vinN) encodes a protein consisting of 478 amino acids. The sequence shown in SEQ ID No. 18 in the sequence listing represents predicted amino acid sequence encoded by the vinN gene. As will be detailed later, that protein is assumed to be long chain fatty acid-CoA ligase.

[0049] In the SEQ ID No. 1 in the sequence listing, bases Nos. 45589-46833 represents an ORF and the gene corresponding to the ORF (vinO) encodes a protein consisting of 414 amino acids. The sequence shown in SEQ ID No. 19 in the sequence listing represents predicted amino acid sequence encoded by the vinO gene. As will be detailed later, that protein is assumed to be PLP-dependent decarboxylase.

[0050] In the SEQ ID No. 1 in the sequence listing, bases Nos. 46982-64492 represents an ORF and the gene corresponding to the ORF (vinP1) encodes a protein consisting of 5836 amino acids. The sequence shown in SEQ ID No. 20 in the sequence listing represents predicted amino acid sequence encoded by the vinP1 gene. As will be detailed later, that protein is assumed to be polyketide synthase module.

[0051] The vin gene cluster is consisted of these genes and the proteins encoded by the gene cluster are involved in vicenistatin biosynthesis. Information on this gene cluster is useful for efficient production of vicenistatin, as well as for tools available for development of novel antibiotics. Therefore, this invention provides a great opportunity for development of novel useful substances.

EXAMPLES Example 1 Screening of 4,6-dehydratase Gene

[0052] Deoxysugars are ubiquitously present in bacterial systems as a constituent of the cell wall or of secondary metabolites. Indeed, deoxysugars are present in many kinds of antibiotics such as macrolides and anthracylines. List of known deoxysugars include, for example, mycarose and desosamine contained in erythromycin, daunosamine contained in daunorubicin, mikamynose contained in tyrosine, and vancosamine contained in vancomycin, etc. Many deoxysugars play an important role in exerting the activity of those antibiotics.

[0053] Recently, many studies have been made on biosynthesis of 2,6-deoxysugars, and the biosynthesis of various deoxysugars is generally believed to proceed as follows: glucose-1-phosphate is metabolized to NDP-glucose by NDP-glucose synthase; the latter is then deoxygenated at C-6 by NDP-glucose-4,6-dehydratase to yield NDP-4-keto-6-deoxy glucose; and it is further deoxygenated at C-2 by NDP-4-keto-6-deoxy glucose 2,3-dehydratase. This sequence is the common pathway of 2,6-deoxysugar biosynthesis, and various 2,6-deoxysugars are assumed to be biosynthesized as the result of further modification.

[0054] Many genes involved in biosynthesis of various deoxysugars have been cloned. In biosynthetic pathway of 2,6-deoxysugars, it was demonstrated that the genes coding for 4,6-dehydratase and 2,3-dehydratase revealed to exhibit high homology with respective congeners. Thus they serve as a powerful tool for cloning of genes involved in the production of the secondary metabolite products.

[0055] Based on a study using labeled precursors, it was confirmed that vicenisamine was derived from glucose. Therefore, it was predicted that vicenisamine would also take the same biosynthetic pathway similar to other 2,6-deoxysugars. Thus, the inventors presumed that a gene responsible for biosynthesis of vicenistatin would be cloned by utilizing a gene responsible for biosynthesis of deoxysugar as a probe. Thus, the inventors utilized a gene coding for 4,6-dehyratase as a probe for screening on a genomic library, because the 4,6-dehyratase gene exhibited high homology among corresponding genes.

[0056] (Design of Primers)

[0057] Gene coding for 4,6-dehydratase exhibited very high homology among corresponding genes. In the base sequences of 4,6-dehydratase, the regions of 46DH-1 and 46DH-2 were known to be conserved in their sequences. It was expected that if sense and anti-sense primers were designed based on the base sequences of 46DH-1 and 46DH-2 and the two primers were used in PCR, a DNA fragment of 530 bp would be amplified.

[0058] 46DH-1: 5′-ACSGGYCSBGCCGCHTTCATCGG-3′

[0059] 46DH-2: 5′-GRWRCTGRTRSGGCCGTAGTTGTT-3′

[0060] (where S represents C or G; Y represents C or T; B represents C, G or T; H represents A, C or T; R represents A or G; and W represents A or T.)

[0061] (PCR Using Genomic DNA as a Template)

[0062] To perform screening on genomic library directed to isolation of clones containing a gene coding for 4,6-dehydratase, it is necessary to confirm whether 4,6-dehydratase gene is specifically amplified using the designed primers. At first, PCR was conducted using a genome of Streptomyces halstedii HC34 (S. halstedii) as a template, for this purpose. PCR condition consisted of 30 cycles with a cycle of 94° C. for 7 minutes, 94° C. for 30 seconds, 52° C. for 30 seconds, and 72° C. for 60 seconds, which was lastly followed by 72° C. for 7 minutes. As a result of the PCR, a DNA fragment having an expected size (about 530 bp) was obtained.

[0063] (Sequencing of the PCR Product)

[0064] The DNA fragment obtained by PCR was subcloned into a pT7Blue T vector, which was then introduced into E. coli. Plasmids were isolated on the obtained transformants and the sequences were confirmed to obtain three sequences of 46DH-A, 46DH-B and 46DH-C. The inventors performed homology search on the databases, and found that these sequences commonly exhibited high homology with known 4,6-dehydratase genes. From this, it was confirmed that the designed primers enabled the specific amplification of the gene encoding 4,6-dehydratase and that they could be used for screening of genomic library in the search of the target gene. It was predicted that any one of the three sequences was obtained by amplifying a gene involved in biosynthesis of vicenistatin. Next, a genomic library was screened using 46DH-1 and 46DH-2 as primers.

[0065] (Screening of the Genomic Library)

[0066] A genomic library derived from S. halstedii HC34 was constructed as follows. A genomic library is a population of DNA clones obtained by cutting the chromosomal DNA of a living organism into fragments having an appropriate length, and subcloning of these fragments into a vector. Each DNA fragment comprises a part of the genome chosen at random. To prepare a genomic library of S. halstedii HC34, the genome of S. halstedii HC34 was randomly digested with Sau3AI, and DNA fragments having a length of approximately 40 kbp were subcloned into a cosmid vector pOJ446, which gave a total population of 6048 clones. They were subdivided into 63 pools of 96 clones and they were stored as the divided 63 pools, otherwise the target gene has to be cloned from enormous amount of 6048 clones.

[0067] (Primary Screening)

[0068] Primary screening by PCR was conducted on the 63 pools in order to screen pools containing a gene encoding 4,6-dehydratase. Using a library fraction contained in each pool as a template, PCR was conducted with 46DH-1 and 46DH-2 as primers, and pools exhibiting amplification of DNA fragment of the purpose having a size of 530 bp were selected as a positive candidate. Thus, 30 pools were found to be positive.

[0069] In the same manner, PCR primers of 23DH-1 and 23DH-2 were designed from dTDP-4-keto-6-deoxyglucose 2,3-dehydratase gene, which was known to have high homology among cognate genes, and PCR based on the primers was conducted using the genome as a template. As a consequence, two kinds of base sequences (23DH-A and 23DH-B) were confirmed and both of which exhibited high homology with known 2,3-dehydratase genes. When the library was screened using these primers, 17 positive clones were obtained. The sequences of 23DH-1 and 23DH-2 are as shown below. 23DH-1: 5′-AGGCCACCCGSAGCAACTACAC-3′ 23DH-2: 5′-GAASCGSCCGCCCTCCTCSGA-3′

[0070] In general, genes involved in biosynthesis of secondary metabolites in microorganisms tends to form a cluster. Therefore, it was expected that the genes encoding 4,6-dehydratase and 2,3-dehydratase, both of which are involved in the synthesis of vicenistatin, would exist close to each other, and thus the two genes of the purpose might exist in a same cosmid. Therefore, nine pools containing the two genes were selected as positive candidates.

[0071] (Secondary Screening)

[0072] PCR for the secondary screening proceeded in the same manner as in the first screening. In the secondary screening, those containing two genes of 4,6-dehydratase gene and 2,3-dehydratase gene were selected as positive. As a consequence, two cosmid clones (K1B10 and K1D11) were isolated.

[0073] (Classification of Positive Clones)

[0074] As described above, the two cosmids of K1B10 and K1D11 contained 4,6-dehydratase gene and 2,3-dehydratase gene. Based on sequence result of the PCR products, it was demonstrated that there are three kinds of genes (46DH-A, 46DH-B and 46DH-C) and two kinds of genes (23DH-A and 23DH-B) coding for 4,6-dehydratase and 2,3-dehydratase respectively, existing on the genome. Thus, the inventors confirmed on what kind of 4,6-dehydratase and 2,3-dehydratase correspond to those contained in the K1B10 and the K1D11, respectively. For this purpose, the inventors performed PCR using each cosmid as a template, PCR products were subcloned into an appropriate vector, then the clones were sequenced. As a result, they found that 4,6-dehydratase gene and 2,3-dehydratase gene contained in the K1B10 correspond to 46DH-A and 23DH-A, respectively. In the same manner it was revealed that 4,6-dehydratase gene and 2,3-dehydratase gene contained in the K1D11 correspond to 46DH-B and 23DH-B, respectively.

[0075] From this, it was suggested that the two cosmids represented different portions of the genome. It had been known that there were two kinds of genes coding for 2,3-dehydratase in the genome, and cosmids containing respective 2,3-dehydratase genes were cloned. Therefore, it was expected that genes responsible for vicenistatin biosynthesis were likely to exist either in the cosmid K1B10 or in the cosmid K1D11. Thus, the inventors proceeded to the analysis of the two cosmids.

[0076] (Estimation on the Genes Contained in the Positive Clones)

[0077] The two cosmids contained different kinds of genes coding for 4,6-dehydratase and 2,3-dehydratase, thus, it was assumed that the genes were involved in the biosynthesis of two different 2,6-deoxysugars. It was suggested that one of the 2,6-deoxysugars was vicenisamine, and that regions adjacent to 4,6-dehydratase gene and 2,3-dehydratase gene in the cosmids K1B10 and K1D11 might contain other genes coding for the enzymes involved in biosynthesis of vicenisamine. The inventors tried to confirm which one of the two cosmids contained genes encoding for enzyme catalyzing biosynthesis of the deoxysugar and involved in biosynthetic system of vicenistatin.

[0078] Each cosmid had been prepared to have an insert size of about 40 kbp. Thus, it was not easy to sequence the total insert at one time. Therefore, an attempt was made to estimate what gene is contained in each of the cosmid. For this purpose, the cosmid was digested with restriction enzymes, and the resulting DNA fragments were subcloned into an appropriate vector, then the clones were sequenced.

[0079] Firstly, the cosmid K1B10 was cleaved with BamHI, BglII and EcoRI, the resulting DNA fragments were subcloned. The cosmid K1B10 was found to contain base sequences having high homologies with those coding for NDP-glucose 4,6-dehydratase, NDP-4-keto-6-deoxyglucose 2,3-dehydratase, NDP-hexose aminotransferase, and NDP-aminohexose-N-methyltransferase. The cosmid also contained sequences having high homologies with those for PKS (polyketide synthase) module I and glutamate mutase. On the other hand, the cosmid K1D10 was found to contain base sequences having high homologies with those for PKS module I and gycosyltransferase. It further contained a sequence having high homology with that for cytochrome P450.

[0080] Comparison of the genes contained in the two cosmids revealed that the cosmid K1B10 contained the genes coding for aminotransferase and for methyltransferase, both of which were considered to be involved in the biosynthesis of vicenisamine, as well as the gene for glutamate mutase which was predicted to be involved in biosynthesis of vicenistatin starter. From this it was suggested that genes existing in the region adjacent to the cosmid K1B10 were involved in the biosynthesis of vicenistatin.

Example 2 Sequencing of Gene Cluster

[0081] Then, regions in and adjacent to the cosmid K1B10 were sequenced to obtain the entire sequence involved in biosynthesis of vicenistatin. Cosmid clones adjacent to the cosmid K1B10 were obtained, and the clones were sequenced. The base sequence data obtained were translated into amino acid sequences, and their functions of the respective genes were estimated by performing homology search based on public database (BLAST).

[0082] (Sequencing of the Cosmid)

[0083] A DNA sequencer reveals, at each run, the sequence of a DNA fragment having a length of about 600 to 700 bp at maximum. The cosmids derived from genomic library of S. halstedii HC34 was produced to contain the insert having length of about 40 kbp. In order to sequence the insert having such a large size, it was necessary to cut the cosmid DNA into fragments having an appropriate size, and to subclone the fragments into an appropriate vector. If the cosmid DNA was cut into small fragments having a length of about 500 bp, the base sequence of the both chains could be sequenced. However, in such case, identification of the restriction sites would be very difficult and ligation of respective fragments would become an excessive work. To cope with this, each insert of 40 kbp was cleaved with an appropriately chosen restriction enzyme into fragments of about 2 to 10 kbp; the fragments were subcloned into a vector; the clones were sequenced; and the thus obtained sequences were ligated properly.

[0084] An EZ::TN<KAN-2> insertion kit enables random insertion of a transposon into a plasmid. By using primers specific to both ends of a transposon, sequence can be determined on the regions adjacent to the inserted transposon.

[0085] Then under the presence of both of template plasmid DNA and transposon, the transposon is inserted in by transposase, and E. coli is transformed by the plasmid DNA. Since kanamycin-resistance gene is encoded on the transposon, it is assumed that the transformants containing template plasmid containing the inserted transposon may exhibit resistance to kanamycin. Therefore, transformants of the purpose can be selected based on the kanamycin-resistance. The transformants containing the plasmid are cultivated, and the sequence was determined using the purified plasmid as a template. This method is appropriate for analyzing a DNA fragment having a length of about 2 to 10 kbp. Thus, the inventors confirmed overall sequences of the respective fragments obtained by restriction enzyme treatment of K1B10, and ligated these fragments.

[0086] (Acquisition of Cosmids Adjacent to K1B10)

[0087] The sequence data of the K1B10 revealed that both ends of its insert contained base sequences having high homologies with TDP-glucose synthase and glutamate mutase. These enzymes were likely to be involved in biosynthesis of vicenistatin, and it was expected that gene cluster involved in vicenistatin biosynthesis would be extended to outside of this region.

[0088] Thus, an attempt was made to obtain other cosmid clones having regions adjacent to the K1B10. Firstly, an attempt was made to obtain cosmids containing left region of the K1B10. Therefore, based on the base sequence of K1B10C1 existing left end of the K1B10C1 insert, specific PCR primers (K1B10-leftF, K1B10-leftR) were designed, and genomic library was screened again by PCR using these primers. Primary and secondary screenings were performed as above to obtain cosmid Y3D4. Furthermore, in the same manner with the left end, PCR primers designed for the right end of the cosmid K1B10 based on the base sequence of K1B10AS (K1B1O-rightF, K1B10-rightR), and they were used for screening and cosmid K7G3 was obtained. Further primers were designed based on the K7G3 and screened, and cosmid L6D5 was obtained.

Example 3 Homology Analysis of ORFs

[0089] Base sequence was determined on the approximately 60 bp region existing adjacent to the cosmid K1B10. When a base sequence is translated into amino acid sequence, six different frames can be given in total, that is, three frames for the forward direction and three frames for the reverse direction, respectively. In general, a prokaryote has a region of about 5 bp with abundant A (adenine) and G (guanine), existing about 10 bp upstream from the start codon, and this region is called Shine-Dalgarno (SD) sequence. It is known that ribosome binds to this region to initiate translation. Therefore, based on this knowledge, the inventors analyzed on ORFs encoding for amino acid sequences.

[0090] However, as to actinomycetes, it is known that the SD sequence does not necessarily exist in the organisms. Therefore, an alternative method is known, that is, the frame can be analyzed by calculating GC content in the frame. The chromosomal DNA of actynomycetes usually exhibits high GC content of 70% or more in the average. However, contents of amino acids corresponding to codons comprising only GC, namely arginine, glycine, proline and alanine, are not significantly higher compared with those of other prokaryotes. The third base of a triplet codon is not practically important to determine amino acid encoded by the codon, and GC content in the third base of the triplet codon is extremely high (90% or higher), while GC content for the second base is very low (about 50%) and that for the first base is about 70%. Moreover, as to region not translated to corresponding amino acid, such as promoter, GC content in the region is about 50%. For example, GC content is analyzed on the 5 kbp region existing left end of the K1B10 using a computer program of Frame Plot. As a result, four ORFs (orfA, orfB, orfC and orfP2) were revealed to exist in the region.

[0091] In the same manner, frame analysis was performed on the all regions to confirm existence of 18 ORFs. FIG. 1 shows a gene mapping obtained in the present experiment. Homology search was performed for the respective ORFs by public databases (BLAST), based on its putative amino acid sequence. Proteins revealed the highest homologies were listed in FIG. 2.

[0092] (Homology Analysis of orfA)

[0093] The orfA consisted of 1068 bp, and was estimated to represent a protein comprising 355 aa (amino acids, that is, the number of amino acid residues) having a molecular weight of about 38 kDa. The orfA corresponds with the vinA gene described above. As a result of the search through databases (BLAST), the protein encoded by the orfA exhibited 69% homology with MtmD (protein ID T48866: glucose-1-phosphate thymidylyl transferase), which is contained in gene cluster of S. argillaceus, and involved in biosynthesis of mithramycin. Moreover, the protein encoded by the orfA exhibited 67% homology with StrD (protein ID A26984: glucose-1-phosphate thymidylyl transferase) of S. griseus which is involved in biosynthesis of streptomycin. Besides, it exhibited high homologies with dTDP-glucose synthases of various secondary metabolites.

[0094] (Homology Analysis of orfB)

[0095] The orfB consisted of 972 bp, and was estimated to represent a protein comprising 323 aa having a molecular weight of about 36 kDa. The orfB corresponds with the vinB gene described above. As a result of database search, the protein encoded by the orfB exhibited high homology with dTDP-glucose-4,6-dehydratase of various Streptomyces species. This enzyme is involved in deoxygenation of a sugar at C-6.

[0096] The orfC consisted of 1260 bp, and was estimated to represent a protein comprising 419 aa having a molecular weight of about 46 kDa. The orfC corresponds with the vinC gene described above. As a result of database search, the protein encoded by the orfC exhibited high homology with various glycosyltransferases.

[0097] All of the proteins exhibited high homology with the orfC are glycosyltransferase of 2,6-deoxysugars involved in biosynthesis of antibiotics. It is known that these enzymes contain conserved amino acid sequences of DXD and LPXCXXhhHHGGXGXXXhAhbXGhPQbbP (where X represents an arbitrary amino acid residue and h represents a hydrophobic amino acid residue). The protein encoded by the orfC also contained these sequences, and from this it was estimated that the protein would be a glycosyltransferase of 2,6-deoxysugars. Furthermore, as the protein had high homology with glycosyltransferase of aminosugars (particularly among 2,6-deoxysugars), it was suggested that the protein serves as glycosyltransferase in the biosynthesis of vicenistatin.

[0098] (Homology Analysis of orfD)

[0099] The orfD consisted of 1482 bp, and was estimated to represent a protein comprising 493 aa having molecular weight of about 55 kDa. The orfD corresponds with the vinD gene described above. As a result of database search, the protein encoded by the orfD exhibited high homology with known dTDP-4-keto-6-deoxyglucose 2,3-dehydratase. For example, the protein exhibited 61% homology with SnogH (protein ID CAA12009: estimated 2,3-dehydratase) derived from S. nogalater).

[0100] (Homology Analysis of orfE)

[0101] The orfE consisted of 993 bp, and was estimated to represent a protein comprising 330 aa having molecular weight of about 36 kDa. The orfE corresponds with the vinE gene described above. As a result of database search, the protein encoded by the orfE exhibited high homology with known dTDP-4-keto-6-deoxyhexose 2,3-reductase, i.e. it exhibited 60% homology with TylCVI (protein ID AAD41821, S. fradiae). This enzyme is involved in reduction of sugar at C-3 position, and is believed to be also involved in the reduction of sugar at C-3 position in vicenistatin biosynthesis.

[0102] (Homology Analysis of orfF)

[0103] The orfF consisted of 1194 bp, and was estimated to represent a protein comprising 397 aa having molecular weight of about 43 kDa. The orfF corresponds with the vinF gene described above. As a result of database search, the protein encoded by the orfF exhibited high homology with aminotransferases involved in biosynthesis of various aminosugars. For example, the protein exhibited 48% homology with EryCIV (protein ID CAA72084) aminotransferase involved in biosynthesis of desosamine, which is an aminosugar constituting erythromycin produced by Saccharopolyspora erythraea, and exhibited 37% homology with VioA (protein ID AAD44154) involved in biosynthesis of 4-amino-2,6-dideoxyglucose produced by E. coli. From these facts it was estimated that the orfF is an enzyme participating in amino group introduction in vicenistatin biosynthesis.

[0104] (Homology Analysis of orfG)

[0105] The orfG consisted of 711 bp, and was estimated to represent a protein comprising 236 aa having molecular weight of about 26 kDa. The orfG corresponds with the vinG gene described above. As a result of database search, the protein encoded by the orfG exhibited 45% homology with methyltransferases utilizing S-adenosylmethionine as the methyl group donor, e.g., the protein exhibited 45% homology with methyltransferase AknX2 (protein ID AAF73460) from S. gallilaeus, and the protein exhibited 44% homology with methyltransferase EryCVI (protein ID CAA72082), which is involved in biosynthesis of desosamine and derived from Saccharopolyspora erythraea. From a study using labeled methionine, it is known that the N-methyl group of vicenisamine is derived from S-adenosylmethionine. From these observations, it was estimated that the protein encoded by the orfG is methyltransferase involved in vicenisamine biosynthesis.

[0106] (Homology Analysis of orfH and orfI)

[0107] The orfH consisted of 477 bp, and was estimated to represent a protein comprising 158 aa having molecular weight of about 17 kDa. The orfI consisted of 1410 bp, and was estimated to represent a protein comprising 469 aa having molecular weight of about 50 kDa. The orfH corresponds with the vinH gene described above while the orfI corresponds with the vinI gene described above. As a result of databases search, the protein encoded by the orfH exhibited high homology with S-subunit of glutamate mutase, while the protein encoded by the orfI exhibited high homology with E-subunit of glutamate mutase. Glutaminate mutase is a unique enzyme in that it isomerises glutamate into 3-methylaspartate utilizing vitamin B12 (adenosylcobalamin) as a coenzyme.

[0108] X-ray crystallographic analysis on site-directed mutated enzymes was performed on GlmE, S (accession number, X80997) of Clostridium cochlearium. The study revealed that His16 of the S-subunit serves as a binding site for the coenzyme, and that Glu171 of the E-subunit serves to recognize the amino group of glutamic acid. In addition, these amino acids are preserved in the protein encoded by the orfI. It has been known that glutamate and 3-methylaspartate are produced as intermediates in vicenistatin biosynthesis, as described above. This suggests that the proteins encoded by the orfH and orfI may catalyze the aforementioned reaction.

[0109] (Homology Analysis of orfJ) The orfJ consisted of 900 bp, and was estimated to represent a protein comprising 299 aa having molecular weight of about 34 kDa. The orfJ corresponds with the vinJ gene described above. As a result of database search, the protein encoded by the orfJ exhibited 54% homology with proline iminopeptidase from Mesorhizobium loti. Besides, it exhibited high homology with proline iminopeptidase from various microorganisms. Contribution of orfJ in vicenistatin biosynthesis could not be predicted only from the homology analysis. However, generally in microorganisms, genes coding for microbial secondary metabolites form a cluster, and thus it seemed possible that this protein might be involved in the biosynthesis of vicenistatin in some way. Gene disruption experiment of the orfJ will be requisite to elucidate the function of this protein in vicenistatin biosynthesis.

[0110] (Homology analysis of orfK)

[0111] The orfK consisted of 984 bp, and was estimated to represent a protein comprising 327 aa having molecular weight of about 36 kDa. The orfK corresponds with the vinK gene described above. As a result of database search, the protein encoded by orfK exhibited homology with acyl CoA-ACP (acyl carrier protein) transacylase of type-II fatty acid synthases derive from various species. When an amino acid serving as a starter unit in the biosynthesis of vicenistatin is incorporated into a polyketide synthase (PKS), this enzyme is considered to catalyze conversion of the CoA derivatives of amino acids into the corresponding ACP derivatives.

[0112] (Homology Analysis of orfL)

[0113] The orfL consisted of 249 bp, and was estimated to represent a protein comprising 82 aa having molecular weight of about 9.6 kDa. The orfL corresponds with the vinL gene described above. As a result of databases search, the protein encoded by the orfL exhibited homology with known ACP. This protein is considered to serve as an ACP to which a glutamate derivative binds, when the derivative is captured by PKS.

[0114] (Homology Analysis of orfM)

[0115] The orfM consisted of 1575 bp, and was estimated to represent a protein comprising 524 aa having molecular weight of about 56 kDa. The orfM corresponds with the vinM gene described above. As a result of database search, the protein encoded by orfM exhibited homology with adenylation domain A (A domain) of type I non-ribosomal peptide synthetase. It was considered that the protein could be involved in activation of amino acids in vicenistatin biosynthesis, that is, in isomerization of the amino acid at biosynthesis of the starter unit or in the formation of macrolactam. If the function of this enzyme is elucidated through further study utilizing gene disruption experiments and overexpression of the enzyme, it will provide interesting results.

[0116] (Homology Analysis of orfN)

[0117] The orfN consisted of 1437 bp, and was estimated to represent a protein comprising 478 aa having a molecular weight of about 52 kDa. The orfN corresponds with the vinN gene described above. As a result of database search, the protein encoded by the orfN was found to have homology with some CoA ligases, i.e., it exhibited 33% homology with estimated long chain fatty acid CoA ligase from Sinorhizobium meliloti, that is, SMb20650 (protein ID CAC49758). On the basis of a study using a labeled starter unit, it is believed that when 3-methylaspartic acid is captured by PKS, it undergoes decarboxylation and isomerization. The capture by PKS may involve the following steps: 3-methylaspartic acid is converted by CoA ligase into a CoA derivative which is then converted into an ACP derivative by the protein encoded by the orfK; and the ACP derivative is captured by PKS.

[0118] (Homology Analysis of orfO)

[0119] The orfO consisted of 1245 bp, and was estimated to represent a protein comprising 414 aa. The orfO corresponds with the vinO gene described above. As a result of database search, the protein encoded by the orfO was found to have a homology with decarboxylase utilized as a coenzyme pyridoxal-5′-phosphate, PLP. It had a highest homology (identity 31%, positive 51%) with BtrK (protein ID BAB18473, Bacillus circulans), which had been suggested to be involved in the biosynthesis of butirosin. Besides, the protein exhibited homology with diaminopimelate decarboxylase and ornithine decarboxylase, which had been believed to be involved in the primary metabolism. It was estimated from the level of homology that the protein encoded by the orfO is decarboxylase involved in the biosynthesis of secondary metabolites, but is rather different from decarboxylase involved in the primary metabolites. From the above results, it is suggested that the protein encoded by orfO may catalyze the expected decarboxylation of a starter unit in vicenistatin biosynthesis.

[0120] (Homology Analysis of orfs P1, P2, P3 and P4)

[0121] As a result homology analysis by database search, the proteins encoded by orfs P1, P2, P3 and P4 exhibited homology with type I PKSs. The orfs P1, P2, P3 and P4 correspond to previously described vinP1, vinP2, vinP3 and vinP4 genes, respectively. The amino acid sequences of the proteins were compared with other PKSs, and it was estimated that the orfP1 is comprised from three modules, orfP2 one module, orfP3 two modules, and orfP4 two modules.

[0122] Among functional domains of PKS, it is known that sequence analysis of AT domain enables to determine whether the extension unit is acetate or propionate. In malonyltransferase (MT) utilizing acetate as the extension unit, two motifs of XYAQXXXXXXQXAL and GHSI (where X represents an arbitrarily chosen amino acid residue) are preserved adjacent to its active site. On the other hand, in methylmalonyltransferase (MMT) utilizing propionate as the extension unit, two motifs of VDVVQXXXXXXMXSLA and GHSQ exist adjacent to the active site. The AT domains of the modules contained in the orfP1 included MT, MT and MMT, that in the orfP2 included MMT, those in the orfP3 included MT and MMT, and those in the orfP4 included MT and MT, in this order.

[0123] Assuming that the orfs P1, P2, P3 and P4 are extended in the order to exert their enzymatic action, the sequential order of the functional domain in the respective modules coincides with carbon backbone constituting aglycon of vicenistatin. Ultimately, the polyketide may be released from the enzyme by thioesterase (TE) domain existing on the OrfP4 to be converted into a ring (FIG. 3). This strongly suggests that the PKS genes concerned here are those responsible for the biosynthesis of vicenistatin. FIG. 4 summarizes the reactions catalyzed by the enzymes encoded by respective vin genes.

[0124] The base sequence analysis suggested that the proteins represented by orfs A, B, D, E, F and G are involved in the biosynthesis of vicenisamine, and that orfC encodes glycosyltransferase for deoxysugars. In addition, it suggested that the proteins represented by orfs H, I, K, L, N, O, P1, P2, P3, and P4 are involved in the biosynthesis of aglycon of vicenistatin. It was expected that these enzymes serve in this sequential order for biosynthesis of vicenistatin. Based on these observations, it was strongly suggested that the genes obtained through the above study should be responsible for the biosynthesis of vicenistatin. The predicted pathway of vicenistatin biosynthesis is summarized in the scheme shown in FIG. 4.

[0125] The proteins represented by 18 ORFs identified in this study did not include that possibly serving as isomerase for 3-methylaspartate, but any one enzyme bearing the activity may serve as an isomerase. Alternatively, the proteins represented by the Orf M and Orf J whose function could not be identified in this study might be involved in this function. Otherwise, the ORF concerned for this reaction might exist outside of the region analysed in this study.

Example 4 Expression of vinC by Recombinant E. coli

[0126] VinC was amplified from the cosmid K1B10 by PCR using two oligonucleotids (oligo EXPRESS SELECT), that is, vinC-N term (5′-AAGGTACCATATGCGCGTCCTGATGA-3′) and vinC-C term (5′-CCCGGATCCGCTGGGCGGAGTGCTAC-3′). The NdeI and BamHI sites inserted into the oligonucleotides are underlined. The used DNA polymerase was Takara Ex-Taq (Takara). The PCR conditions consisted of 30 cycles with a cycle of 95° C. for 7 minutes, 95° C. 30 for seconds, 56° C. for 30 seconds, and 72° C. for 90 seconds, followed by 72° C. for 7 minutes.

[0127] The PCR product was cloned into pT7Blue T vector; the sequence of the clones was confirmed and clones containing proper sequence were selected. VinC was cloned using NdeI and BamHI sites and cloned into pET30b(+) to produce pET-vinC. The obtained pET-vinC was used to transform E. coli BL21 (DE3), to produce recombinant E. coli cells for expression of vinC. The recombinant E. coli cells thus obtained were designated as BL21(DE3)/pETvinC. The procedures for conventional gene manipulation was performed in accordance with the description of “Molecular Cloning” written by Joseph Sambrook and David W. Russell, Cold Spring Harbor Laboratory Press.

Example 5 Confirmation on Enzymatic Activity of the Recombinant VinC

[0128] A cell-free extract was prepared from the cells of E. coli obtained as described for VinC expression and it was used as a crude enzyme solution. Then glycosyltransferase activity of the enzyme solution was confirmed using dTDP-vicenisamine as a substrate. The method to produce starting materials used in the enzyme reaction, and the result of the enzymatic activity will be described below. FIG. 5 shows the scheme for synthesis of dTDP-vicenisamine, dTDP-2-mycarose, and dTDP-2-deoxyglucose, used as substrates of the enzymatic reactions.

[0129] (Preparation of dTDP-Na Salt)

[0130] Sodium salt of dTDP (100 mg) was dissolved in cold water, and the solution was passed through a column filled with H⁺ type DOWEX AG-50 X8. Into the fraction containing the target substance having pH of 1 to 2, an aqueous solution of 4% tetrabutylammonium hydroxide (Bu₄N—OH) was added until the pH reached to 5 to 6. The solution was freeze-dried and a white crystalline substance was obtained.

[0131] (Synthesis of dTDP-vicenisamine)

[0132] The synthesized compound (1) (41.5 mg, 1.41×10⁻⁴ mol) was dissolved into 2 ml of CH₂Cl₂, and the solution was transferred into a bath containing acetone-dry ice and kept at −10° C. Into the solution, Et₃N (0.392 ml, 2.81×10⁻³ mol, 20 mol eq.) was added, and then TMS-Cl (0.213 ml, 1.68×10⁻³ mol, 12 mol eq.) was added. After stirring for 30 min, 0.4 ml of Et₃N and 0.2 ml of TMS-Cl were added. After another 30 min stirring, 0.2 ml of Et₃N and 0.1 ml of TMS-Cl were further added to the mixture. After stirring for 1.8 hour, the solution was concentrated with an evaporator.

[0133] To the residue, a solution of pentane/ethyl acetate (EA)=4 was added; the resulting solution was filtered and concentrated; and benzene was added to the solution followed by azeotropic evaporation, to give a solid. Then 1.2 ml of CH₂Cl₂ was added to the solid and it was kept at −78° C., to which was added TMS-I (0.026 ml, 1.83×⁻⁴ mol, 1.3 mol eq.). Forty-five minutes later, the resultant was added to a mixture containing dTDP-Bu₄N salt and 20 μl of diisopropylethylamine (DIEA) dissolved in 1.5 ml of CH₂Cl₂.

[0134] The solution was stirred for 1.5 hour, and then its temperature was gradually raised. After 1.3 hour, 120 μl of tetrabutylammonium fluoride (TBAF) was added to the solution. After 55 min of stirring, the solution was concentrated, and the concentrate was purified by reverse phase silica gel chromatography (water:methanol=1:1->1:5) to yield 103 mg of partially-purified sample. A solution of water:methanol=1:1 (7 ml in total) was added to the sample. To the solution, it was added with 11.3 mg of Pd/C, and the whole was subjected to hydrogenolysis in hydrogen atmosphere. After the reaction was completed, the mixture was filtered and concentrated. The concentrate was purified with a DEAE Sephadex column A-25 equillibated with 30 ml of NH₄HCO₃ solution to yield 13.2 mg (two steps, 16%) of dTDP-vicenisamine diammonium salt (compound (3)) in the form of white powder.

[0135] MS data: [C₁₇H₂₉N₃O₃P₂-H]-, and calculated MW: 544.11, measured MW: 544.2 (base peak)

[0136] Synthesis of ADP-vicenisamine and UDP-vicenisamine was performed by the process according to the procedure described above.

[0137] (Synthesis of dTDP-mycarose)

[0138] The compound (4) (46.4 mg, 2.86×10⁻⁴ mol) was added to 1 ml of pyridine, and the mixture was kept at 0° C., to which was added TMS-Cl (0.8 ml, 22 mol eq). After 11.5 hours, 7 ml of pentane was added, and cold water was added and then separated. It was washed until the residual pyridine becomes less than detection limit by TLC. The supernatant was concentrated, and the residue was used for further operation. The crude product (compound (5)) was dissolved in 1 ml of CH₂Cl₂, and the solution was kept at −78° C. Then, TMS-I (0.0529 ml, 1.3 mol eq.) was added thereto, and 45 minutes later, a mixture solution of dTDP-Bu₄N salt and 40 μl of DIEA dissolved in CH₂Cl₂ was added to it. After stirring for three hours, 480 μl of TBAF was added thereto, and the mixture was concentrated 40 minutes later. The concentrate was purified via DEAE-Sephadex as above to yield 21.5 mg of dTDP-mycarose (compound (6)).

[0139] (Synthesis of dTDP Derivative of 2-deoxyglucose)

[0140] 2-Deoxyglucose (7)(31.3 mg, 1.91×10⁻⁴ mol) was dissolved into 1 ml of pyridine, to which was added TMS-Cl (0.5 ml, 3.94×10⁻³ mol, 20 mol eq.) at room temperature. After 1.5 hour, 5 ml of pentane was added, then cold water was added and separated. The supernatant was concentrated, and the concentrate was subjected to azeotropic treatment with benzene to afford a TMS derivative (compound (8)).

[0141] To this crude product was added 1 ml of CH₂Cl₂, and the mixture was cooled to −78° C. Then, TMS-I (0.3 ml, 2.48×10⁻⁴, 1.3 mol eq.) was added. Forty minutes later, a mixture (which was obtained by dissolving dTDP-Bu₄N salt and 40 μl of DIEA in CH₂Cl₂) was added. The temperature of the solution was gradually raised, and after stirring for 3.4 hours, 0.1 ml of TBAF was added to the solution. After additional stirring for fifty minutes, the solution was concentrated, and the concentrate was purified by DEAE Sephadex A-25 column.

[0142] (Enzyme Reaction)

[0143] The above-mentioned recombinant E. coli BL21(DE3)/pETvinC was used for pre-culture on 4 ml of LB medium containing kanamycin. Then, a mixture comprising 100 ml of LB medium, 30 μg/ml of kanamycin and 1 ml of the pre-culture was prepared and was incubated for two hours at 37° C. under shaking with 220 rpm. The cultivation continued until OD600 reached to about 0.6. IPTG was added to the culture until the concentration reached to 0.2 mM. The culture was further incubated at 37° C. for about three hours under shaking with 180 rpm. About 400 mg of the recombinant E. coli cells were collected, and a buffer (comprising 50 mM tris-HCl, pH 7.5; 1 mM, MnCl₂; 1 mM, MgCl₂) was added to the cell pellet, at such a volume corresponding to 10 times as much as that of the cell pellet (4 ml of buffer to 400 mg of cell pellet). The cell suspension was sonicated 10 times for two minutes to disrupt the cells. The resultant solution was centrifuged at 12,000 rpm for 30 minutes. The supernatant (cell-free extract) was collected and used as a crude enzyme solution.

[0144] A 14 μl of dTDP-vicenisamine dissolved in distilled water (3.3 mg/700 μl) and 3.6 μl of aglycon (saturated solution in DMSO) were transferred into an Eppendorf tube in an ice bath, and 100 μl of the crude enzyme solution was added thereto, and the mixture was stirred to allow the enzyme reaction to proceed. Twenty-four hours later, distilled EA and 2N NaOH were added to adjust pH of the solution at pH10 or higher. Then, the solution was extracted with ethyl acetate. The extracted supernatant was concentrated with an evaporator, and 30 μl of methanol was added thereto. In the same manner, dTDP-mycarose and dTDP-2-deoxyglucose were allowed to react separately with the aglycon.

[0145] The reaction product was detected with an LC-MS equipment (LCQ type, Finnigan) connected with a HPLC system equipping ODS column (Mightysil RP-18 GP, Kanto Kagaku). The reaction product was detected by UV 254 nm, and its structure was simultaneously analyzed by mass spectrometry. As a result, it was confirmed that the reaction between dTDP-vicenisamine and the aglycon in the presence of the enzyme underwent glycosyl transfer reaction to produce vicenistatin.

[0146] Mass spectral data: [M+H]⁺; calculated MW: 501.36; measured MW: 501.2

[0147] In the same manner, glycosyl transfer reaction between dTDP-mycarose and vicenistatin aglycon was also confirmed.

[0148] Mass spectral data: [M+H]⁺; calculated MW: 502.35; measured MW: 502.3

[0149] Moreover, glycosyl transfer reaction between dTDP-2-deoxyglucose and vicenistatin aglycon was also confirmed.

[0150] Mass spectral data: [M+H]⁺; calculated MW: 504.32; measured MW: 504.1

[0151] These results suggested that the recombinant VinC enzyme produced by the recombinant E. coli exhibited enzymatic activity as a glycosyltransferase. Therefore, it was confirmed that the VinC enzyme derived from the vicenistatin biosynthetic gene cluster plays a role as a glycosyltransferase.

[0152] This invention provides base sequence of the vin gene cluster, which is a cluster of genes encoding an enzyme complex catalyzing biosynthesis of vicenistatin. This invention further provides a transferase (VinC enzyme), which catalyzes synthesis of vicenistatin using dTDP-vicenisamine as a substrate, as well as a gene (vinC gene) encoding the enzyme. The VinC enzyme is useful for enzymatic synthesis of vicenistatin, which is a valuable compound. It is further suggested that use of the VinC enzyme may be useful for synthesis of novel polyketide glycosides.

1 26 1 64492 DNA Streptomyces halstedii sp.HC-34 1 agatctggtg aatccgatgg gcctcgggct gccggagcgt gcgggactcc agctcgctct 60 cgcccggcag taatgcgtcc actgtgacga tttcagcgat atgcgcggct tgatcggcgg 120 gcaggggcac gctccggaag agctgatcca ccacgccgag ttgtagctca cgctctgcct 180 tggccccggt cgccgcgaga tgcagcgcgc ccgagtcgag agcgtggtgt gacagtgcct 240 ccaggagggc agtcttgccg gaggctatgg cgccactgat cagtacggct ctcccgtgcc 300 cccgggtggc gtcacccagc aaccctccca aggcgtgcag ttcctcgtcg cgttccacga 360 acaccatcgt cgcaaccctc tccccgttca gatgtcgcgt acgtacgtat gaatatatcg 420 catgccactt gccgggtgaa tataaatttt actttactta cggattactt gcgctctgtc 480 gtgtcgtcat ggcaagggcg ctcacccttc aacgtaggtg ctacgggccg acataggggc 540 cgccccgggc cgattagggg ttatcccggc cggggccccc gagtaaaaat gctgtcgccg 600 gaccgcggaa aaattcacgg cggcgacgcg acccccaacg gcgtgtcccc gctcctgcgg 660 gtatctctcc agccggctag acctaggggg ttgggtgaaa gcgctcgttt tgtctggcgg 720 atccggtaca cggctccgac cgatcacaca cacatcagcc aaacaactgg tgcccgttgc 780 gaacaagccc atcctgttct acgtcctgga gtcgatcgcc gaagcgggca tcaccgacgt 840 tggcatcgtt gtcggacaca ccgctccgga ggtccaggac gcggtcggtg acggctccgc 900 cttcggggtg gacgtcacct acatcgccca ggacgagccg ctcggcctcg cccacgcggt 960 ccgcatctcc cgcgactacc tcggtgatga cgactttgtc atgttcctcg gtgacaactt 1020 catcatcgac ggcgtcaccg gacttgtcga ccgcttccgt gatgagcgcc ccgacgcgca 1080 gatcctgctg acccgggtcc ccgacccccg ggccttcggc gtcgccgtcc tcgacgaaca 1140 gggccgcgtc atcggcctgg aggagaagcc agaacacccc cgcagcgatc tggcgctcgc 1200 cggcgtctac ttcttcaccc ccctcatcca cgaggccgtc tgggccgtca aaccctcctg 1260 gcgcggcgaa ctggagatca ctgactccat ccagcacctc atcgacaccg gagccgacgt 1320 ccgctcccac atcatcgacg ggtactggaa ggacaccggg aacgtcgtcg acatcctgga 1380 ggtcaaccgc atcatcctgg agagcgtcga gaccgccatc gacggcgacg tcgacgcgga 1440 ctccgagatc atcggccggg tcgtcatcga gaagggcgcc accgtcaagg gctcgcggat 1500 cgtgggcccc gccctcatcg ccaccggaac cgagatccgc gactcctacg tcggaccctt 1560 cacctccgtc gccgagaact gtcgcatcca cgacagcgaa ctggagttct ccatcatgat 1620 gcgggactcg tccctcaccg gcatccgccg catcgaggcg tcgctcatcg gccgccatgt 1680 ccacggcacc gccgtacccc gcgtacccaa cgcccaccgg ctcgtcctcg gcgaccacag 1740 caccttccag atcagctcat gagcacccga ctgctcgtca cgggcgccgc cggattcatc 1800 ggatcggcct acgtccgcgg actcctcacc gaccagcccg acctgcgggt caccgtcctc 1860 gacagcctca cctacgcggg caaccgggcc aacctcgacc tgacacaccc ctccctcgac 1920 ctcgtcgagg gtgacatctg cgacaccgag ctcgtggacc gcctcaccgc cgaagccgac 1980 cagatcgtcc acttcgccgc cgagagccac gtcgaccggt ccatcaccgg ctccgccgag 2040 ttcatccgca ccaacgtcct cggcacccac accctcctcg acgccgcgct ccgccacggc 2100 atcgaccggt tcgtccacat ctccacggac gaggtctacg gatcgatcga gaagggctcc 2160 tggccggaga ccgacccgct gcgccccaac tccccctact cggcgtccaa ggcatccagc 2220 gacctcctgg cgctcgccta ccaccggacc cacgggctcg acgtacgggt cacccgttgc 2280 tccaacaact atggccccta ccagcatccc gagaaggtca tcccgctctt cgtcaccaac 2340 ctcctcgacg gcaagcgggt acccctgtac ggggacggcc agaacgtccg cgactggctg 2400 cacgtcgagg accactgcgc cgccatcgaa tgcgtccgca cccgcggtgg cgccggggag 2460 atctacaaca tcggcggcgg caccgaactg agcaaccggg aactcaccgg cctgctcctg 2520 gaggcgtgcg gggcggactg ggacagcgtg gagtacgtca ccgaccgcaa gggccacgac 2580 ctgcgctact ccgtcgactg gtccaaggtc gccgacctcg gctacacccc cgcccacgac 2640 ttccgtgccg ggctcgcgga gaccgtcgac tggtaccgct ccaaccgcac ctggtgggaa 2700 ccggcgaagt acggccacag ccccgcctga ccggccctac cgccggccga cactcccaca 2760 cccgcacctt cgctcggaga agaaacccca tgcgcgtcct gatgacggtg ttcgccaacc 2820 gctcccacct ctacaacatg gtgcccctcg cctgggccct gaccaccgcg ggccacgagg 2880 tccacatcgc cagccacccc gacaacgtgc aggcgatcag cgacagcggc ctcaccgccg 2940 tacccgtcgg caacgacctc aacatcatgg cgctggcgca gtccaccccg cgcgaggaga 3000 tggtcaacgg cggcgcgctc accctcaacg agacccggcc cgagaagctg acctggcagt 3060 acatccacga cgtgttcgcg cagtactccc agatatacga gtacatggcg gactcgacca 3120 tgaccgccga cctggtcgcc cacgcccgcc agtggcagcc cgacctcgtc atctgggacg 3180 ccctcaccta cgccggcccc atcgccgccg aagccgtcgg cgcaccgcac gtccggatgc 3240 tcttcggcct cgaccagtgg ggccggatgc gcgaccactt caaccggctc accggggaac 3300 gcgccgccga cgaccgccac gacccgctcg ccgactggct cgcaaccaag ggcgagccgc 3360 acggagtggc cttcaccgaa tccctcgtca ccggcacgac caccctcgcg gtcgccccgc 3420 cgtggatgtc gttccccagc gagcagcccg ccctctccat gcggcacctc cccttcaacg 3480 ggcccgccgt gctccccgac tggctccgcg aggcccccag caggccgcgc gtctgcctca 3540 ccctcgggct gaccctgcgt gaactcgccg acgacaacgt caccctcgcc gacttcgtca 3600 acgccgtcgc cgacatcgac gccgacgtcg tggcgacctt ctccgcggaa caggtcgccg 3660 agatcggcga cctgcccgac aacgtccgcg cggtggactt cgtaccccta cacgccctgc 3720 tgccgagctg cgccgcgatc gtccaccacg gcggcggcgg cacccgcacc aacgccatcc 3780 ggtacggggt gccccagctg atcgtcccca actggctctg ggacgagggg tatgtggccg 3840 agcgcttcgc cgagcgtggc gcggcactcg tcaccgaggt ccccgacctc acccccgacc 3900 ggctgcgcga ccagctccgc aggctcatcg ccgagccgtc cttcaaggcg gcggcggagc 3960 agatccagaa ggagtacgac gcgctgccca gcctcaccga gaccgtcggt gagctggtgc 4020 gcgtcgcgga gcgcgggcgc tccctgtagc actccgccca gcggtacggg gggccgctgg 4080 gcggcccgcc gtaccgaggg cgtgacccgt atcgattcgg ccatccttgg cgcggcagac 4140 ccctgccggt ccgctccggg caaccccgag acggggatgg tcctctaagg gggcgtaggg 4200 gttggcggcc cccacccctg cccccgtagc gtgggaatcg ttcaggctcg ctggcgattg 4260 tccaatcaaa tagttaagcc cgtagattcc atcgagcctt ttcgagaact gcgggttcgc 4320 tttgtcgtgc tctccgcacc cgaatcatcg ggtgcccagc agagttccga cagccgctca 4380 ttcaaccgaa cccgtttcac gaggtgatgg cgtggagaac gaaaagaaac ttctcgatta 4440 cctcaagcgg gctaccacgg acctacgtga agcacgccgc cgcctccgcg agatggagga 4500 aaaggaccag gagcccatcg ccatcgtcgg catcggctgc cgctttcccc gcggtgtcga 4560 gtcggcggag cagctctggg acctcgtcgc cgatggcggc gaggcgctca ccccgttccc 4620 cgaggaccgg ggctgggaca ccgacagcct gtaccacccc gacccggagc acctgggcac 4680 cagctacacc aacgtcgggg ccttcctgca cgacgccgcc gagttcgacc ccggcttctt 4740 cgggatctcg ccgcgcgagg ccctcgccat ggacccgcag cagcgactgc tgcttgagac 4800 gtcctgggag gccatggagc gggcgggcat cgacccggcc ggcctgcgcg gcagccgcac 4860 cggtgtcttc acgggtctga tgtacttcga ctacgggtcc cgggtgcact ccgcccccga 4920 ggacatcgag ggctacctcg gcaacggcag cgcgggcagc atcgcgtccg gccgggtcgc 4980 ctacaccttc ggcttcgagg gccccgccgt cacactcgac accgcctgct cgtcgtccct 5040 ggtcgccatc cacctcgccg cgcagtccct gcgcaagggc gagtgcaccc tggcgctggc 5100 cggtggcgcg tcggtgatgt cgacgccgga catcttcgtt gacttcagcc gccagcgggg 5160 tctgtccgcc gacggccggt gcaaggcgtt ctcgtccgac gcggacggta cgggctgggg 5220 cgagggcgtc ggtgtcctgc tgctggagcg gttgtcggac gcgcggaaga acgggcaccg 5280 gatcctgggc ctggtacgcg gctccgccgt caaccaggac ggcgccagca gcggtctgac 5340 ggcgccgaac ggtccttcgc agcagcgggt gatccgccag gcgctggcca acgccggtct 5400 gtcggccgcc gaggtggacg cggtcgaggc gcacggtacg ggtacgaagc tgggtgaccc 5460 gatcgaggcg caggcgctgc tggcgaccta cggccaggag cgggaagagg gccggccgct 5520 ctggctcggt tcgatcaagt cgaatgtggg tcacacgcag gctgccgcgg gtgtcgccgg 5580 tgtgatcaag atggtgctcg cgatgcgggc cggtgtgctg ccgaagacgc tgcatgtgtc 5640 ggagccgtcg ccgcacgtgg actggtccgc cggcgcggtg gaactgctga cggagacgcg 5700 cgactggccg gagaccggcc gtccgcgccg cgccggtgtg tcgtcgttcg gtatcagtgg 5760 cacgaacgcg cacgtcatcg tggagcaggc gcccatggac gaggcgatgg acgaggtggc 5820 cggcgagcgg gagacccctg ccgcggggtc ggaccggacc gtcccgtggg tcatatcggc 5880 gaagtccgcc gacgcgctcc gcgcacaggc cggacggctg agcaccttcc tcgccgggac 5940 cgagggaact ctgactactg gtatttcttc cgaaacttct gtggccgctg tttcagcgga 6000 tgcgtccgcg gttggttggt cgttggtgcg gggtcgttcg gtgttcgcgc atcgggcggt 6060 tgtggtgggt ggtgagtggg acgcgctgct ggcgagtatc ggtgaactgg ccgatggcgc 6120 cgaggatggt tccggtgctg cctctggttc tgttgtgtcg ggtgtggcgg atgtgtcggg 6180 gcgtcgggtg tttgtgttcc cggggcaggg ttcgcagtgg gttggtatgg cgcaggggtt 6240 gttggattcg tcggtgatgt tcacggagcg gatgacggag tgtgctgcgg cgttggatcc 6300 gttggtggag tggtcgttgt tggatgtggt gcggggtgtg gagggtgcgg cgtcgttgga 6360 gcgggtggat gtggtgcagc cggtgttgtg ggcggtgatg gtgtcgttgg cgtcggtgtg 6420 gcgttcggtg ggtgtggtgc cggatgcggt ggtgggtcat tcgcagggtg agatcgcggc 6480 tgctgtggtg ggtggttggt tgtcgttggt ggatggtgcg cgggtggtgg cgttgcggtc 6540 gttggcgatt cgtgaggtgt tggcgggtgg tggtggcatg gtcgcggtcc aggctgcgga 6600 ggatgaggtt gctgggtggc ttgagggtgt ggagggggtg gggattgctg cggtgaatgg 6660 tccgcgttcg gtggtgatct cgggtacgcg tgcgggtttg gatgcgtgtg tggagttgtg 6720 gtctgggcgg gggacgtggg tgaagcgggt tccggtggac tatgcctcgc attcggctga 6780 ggtggagcgg gtgcgtgagc gggtgctggc ggatctggcg agtgtgacgg gtttgtcggg 6840 gtcggtgccg atgttgtcga cgatgacggg tgactggatt gttgagggtc aggttggggc 6900 cgggtattgg gtggagaatc tgcgtcgtcc ggtgttgttc gcggacgcga cgaggcggtt 6960 ggcgtcggag ggtttcggcg cgttcgttga ggtgagtgcg catccggtcc tggtcatggg 7020 catcgaggag acgatcgagg cgctgaggtc gggtgccgcc gatggtgcga agtccggtgc 7080 tggtgaggag agttcctccg ctgtggtggc ggtggggacg ttgcgtcgtg gtgagggtgg 7140 ttgggatcag ttcctgcgtt ccctcgcggg gctcttcgtc cggggtgcgg tgacaccgga 7200 ttgggagtcg ttgttgggtg gtgtgcgtcc tcgggttgat ttgccgacgt atgcgttcca 7260 gcgtgagcgg ttgtggctgg atgcgggtgt ggtggcgggg gatgtgtcgg ggttgggtca 7320 ggtggtggtg ggtcatccgt tgttgggtgc tggtgtgggt gttgctggtg agggtggggg 7380 tgtgttgttt acgggtcgtt tggggttggg ttcgcatccg tggctgggtg atcatgcggt 7440 gtcgggtgtg gtgttgttgc cgggggctgc gtttgtggag ttggtggtgc gtgcgggtga 7500 tgaggtgggg tgtggtcggt tggaggagtt gacgttggcg gctccgttgg tggtgccgga 7560 gcgtggttcg gtgcggattc aggtggtggt gggtgctggt gatgggtcgg gtgcgcgttc 7620 ggtgggtgtg tggtcgtcgg tgggggatga gggtgtgggt ggggagtggg tgtgtcatgc 7680 gtcgggtttg ttgacggctg atgtgggtgt ggcgccggtg ttgggtggtg tgtggccgcc 7740 ggtgggtggt gtggcggtgg atgtgtcggg tgtgtatgag gggttggcgt tggaggggta 7800 tgagtatggg tcggtgtttc gggggttgag gtcggtgtgg cgtcgtgggg atgaggtttt 7860 tgctgaggtg gcgttgggtg agggtgtggg ggtggagggg tttggtttgc atccggcgtt 7920 gttggatgcg gcgttgcagg ctgctgggtt tggttcgttt gtgccggagt ccgaggcagg 7980 gtctgaggcg ggttcgggtg gggtgcggtt gccgttctcg tggtcgggtg tgtcgttgtt 8040 tgcgtcgggt gcttcggtgg ggcgggtgcg gttgtggccg gtgggtgggg atggttttgg 8100 tgtggagttg tttgatgggg tggggatgcc ggtggcgcgg gtggatgcgt tggtgacgcg 8160 ggagattagt gcgggtcagt tgggtgcggc tgctggtgcc gggtcgttgg tgggtgggga 8220 gtcgttgttc cgggtggagt gggctcctgt gtcgggtgtt gcaccggctt ctgctggtgt 8280 gggtggttgt gtggtggtgg gtgcggggag tgtgttgtct ggttttgggg aggtggttcc 8340 ggatctggcg gcggtttccg cgggttctgc ggctgtgccg gggtgggtgt tggtggatgt 8400 ggatgcgtgg ttgggtgcgg atctggcggt gggtgtggtg tcgggtgagg gtgttccggt 8460 ggtggcgcgt ggtgtggtgg cgcgggtgtt ggggttggtg cgggagtggt tgggggatga 8520 gcggtgggtg tcgtcgcggt tggtgtgggt gacgcgtggt gcggtgggtg ctcgggtgtt 8580 ggatgaggtg tcgggtgtgg tgtcgtcggg gttgtggggg ttggtgcggg ctgctcagtc 8640 ggagcatccg gaccggttcg cgcttcttga tctggacagt gccaccgccg tggatgccgt 8700 tcgtgatggt gtgttggggt tgttggctgc tggtgagccg cagttggtgg tgcgtgaggg 8760 tgaggtgctg gccgcacggc tgacccccgc ccacaccacc gacgccctga tccccctcgc 8820 cgaccacgcc ccgtggcgcc tcgccaagga ccccggtggc agccttgacg cgctgacggt 8880 cgtcccggcc cccgacgtac tggagccgct caccgaggga caggtccgca tcgcggtccg 8940 cgccgccggg gtgaacttcc gtgacgtact catggcactc ggcatggtcc ccgcccgggg 9000 tacccagctc ggtggcgagg ccgccggcgt cgtgaccgct gtcggccctg gagtcaccgg 9060 gatcgccgtc ggcgaccgcg tgatgggcgt cttcgacggc ccgttcggcc cggtggccgt 9120 cgcggatcgg cgcatggtct cccgtatccc cgatgcctgg tcgtacaccg aggccgcgac 9180 gatcccgctg gtgtacctca ccgcgtacta cggactggtg gacctcgccg ctctccagca 9240 gggacagcgc atcctggtgc acgccgccac cggtggcgtg ggcatggcag cggtccagct 9300 cgcccgccac ttcggcgccg aggtgtacgg cacggccagc cccggcaagt gggacaccct 9360 gcgcgcgatg ggattcgacg aggcgcatat ggcctcctcg cggtccctcg acttcgagga 9420 ccacttctgg cagacgacgg gtggcgaagg cttcgacgtc gtactcaact ccctcgcgca 9480 ggagtacgtg gatgcttcac tgcggctcca gccgcgcggc ggccgattcc tggagatggg 9540 taagaccgat atccgggacg ccgatgaggt cgcggcggca cacgagggag tgcgctatga 9600 ggcgtacgac ctcaccgtct tcaccagcgt cgacggaccg ggcgcgatcc ccgagcgcat 9660 tcaggagatg ctctccgaac tgcttgcgct gttcgacaag ggagtcctca ccccgctgcc 9720 cgtcaccacc tgggacgtcc gccgcgcgtc cgccgcgctg cggcacatgt cgcaggcccg 9780 gcacaccggc aagatcgcgc tgacggtgcc gcgcccgctc gaccaggacg gcacggtcct 9840 cgtcaccggt ggcaccggtg tcctgggcag tctcctggcc cgtcatctgg tgaccgagca 9900 cggggtacgg aatctgctgc tggtgagccg tcggggcggc gacgcccccg gcgccgccga 9960 actggtcgcc gagctgacgg cagccggtgc cgaggtgagc gtcgtcgcct gtgacaccgc 10020 cgaccgggca gcgttggaga agctcctcgc gtccgtgccg ggtgacgccc cgctgacggg 10080 cgtcttccac acggcgggcg tgctggacga cggaatcgtc gaggcgatga ccccggagcg 10140 ggtggacgcc gtgatgcgcc ccaaggtgga cgcggcctgg catctgcacg agctgaccga 10200 gggacttgat ctcgcggcct tcgtgctcta ctcctccgca gccggtgtct ccggtgacgc 10260 gggccagtcc aactacgccg ccgccaatgt cttcctcgac gccctcgcac agcggcggcg 10320 ggctgccggg ctgcccggcc agtccctcgc ctggggcctg tgggacgacc ggagcgagat 10380 gaccggtcac ctcggcgacg ccgagatcgc ccggatgacc gaggccggtg tcctcggctt 10440 caccgccgcc gacggcctgg ccgcgctgga ccgcgcggcg atgtacgacg acgccgtgct 10500 ggtgccgatg aagctggaca cggcgaccct gggcgcgggc tcgtcgcccg taccgcatct 10560 cttccgcggt ctggtgcgga cccccgtcgt acgccgggcc gtcgccggga acaccggcgg 10620 ggacagcggc ggcggacttg agcagcggct cgccgctctc accgcggccg agcgcaccga 10680 gaccgtgctg gaactcgtac gggagcgcgt cgccgcggtc ctcggacatg ccagcgccga 10740 cgccatcgat cccgcccggg cgttcaagga gatcgggttc gactcgctca cggctgtcga 10800 actgcggaac aggctgaacg cggccaccgg actgcggctg cccgccacac tggtcttcga 10860 ctatccgacg cccacggtgc tctcgcagta cctcctggcg gagctggcac ccggcttgcc 10920 ggccgaggac ccggtcggga cccggctgct ggagcagatc gcccgtatcg aagcggtcct 10980 ctccgaggtc tcggaggtca cggacgagac ctcctccctc tccgacatgg acgccgatgc 11040 ccgatcgggc atcaccgcac gcctcaacga catcctgacc gcatggaaca gggcccagcg 11100 cgcgccgggt cacgacgcgg tcgcggcgga actggacgac gccagcgacg acgaaatctt 11160 cgatttcatc gacagcacct tcggcaagtc ctgactcatc cccgctgacc caccgacgcc 11220 aaccccgcgt ttccgcatac ctggacgggt gaaccactca tggccaacga agccaagctc 11280 cgcgaatacc tcaagcgcgt caccaccgat ctgcacgaga ccaatgagcg cttgcgcgag 11340 gtcgagggca gggcgaacga accgatcgcg atcgtgggta tgagctgccg cttccccggg 11400 ggtgtcgagt ccccggagca gttgtgggag ctgttccgta cgggtacgga cgccatcggt 11460 gagttccccg aaggacgcgg ctgggacgtc gaggggctct accacccgga ccccgaccac 11520 gcgggcacca gctacacgcg tgaaggcggc ttcgtccacg gcgccgagcg cttcgacccg 11580 agcctcttcg gcatctcgcc gcgcgaggcc gtgtcgatgg acccgcagca gcggctgctc 11640 cttgagacct cgtgggaggc cctggaggcg agcggactcg acccgctccg cctcaagggc 11700 agccgcaccg gtgtcttcgt cggtgtcatg tcctcggact acggcattca gaagggctcg 11760 gcgcccgacg gtgtcgaggg cttcctgagc accggtacgc actccagcat cgtctccggc 11820 cgggtctcgt acgtcctggg tctggagggt ccggcggtct cggtcgacac cgcttgctcg 11880 tcctcgctcg tcgccctgca ctccgccgcg cacgccctgc gccagggtga gtgctccctc 11940 gccctggcgg gcggcgtgac gatcatgtcg acgccggaac gtttcgtcga gttcagccga 12000 cagcgggccc tgtccgccga cggccgctgc aaggcgttct cggcgagcgc cgacggcacc 12060 ggctggtccg agggtgtcgg catgttggtc ctggagcggc tctccgacgc gcggaagaac 12120 gggcaccggg tgcttgcggt catccgtggt tcggcgttga accaggatgg tgcgagcaat 12180 ggtctgacgg cgccgaacgg tccgtcccag cagcgggtga ttcgtcaggc gctggcgagt 12240 gccggtctga cggcggccga ggtggacgct gtcgaggcgc atggcaccgg caccacgctc 12300 ggtgacccca ttgaggcgca ggcactgctg gcgacctacg gcaaggagcg cgaggacggt 12360 cgtccgctgc tgctgggttc ctccaagtcg aacctcggcc acacccaggc cgcggccggt 12420 gttgccggtg tgatcaagat ggtgctcgcg atgcgggccg gtgtgctgcc gaagacgctg 12480 catgtgtcgg agccgtcgcc gcacgtggac tggtccgccg gcgcggtgga gctactcacg 12540 gaggcccggg agtggccgga gaccggccgt ccgcgccgcg ccggtgtgtc gtcgttcggg 12600 ttcagtggca cgaacgcgca cgtgatcatc gaggaggcgt cggagttcga gccgagcgcc 12660 gtggagccgc tggccgggtc gggcgtgact ccgccgtggg tgctgtcggc gcggtcggcc 12720 gacgcgttgc gggggcaggc ggagcggctg ctgtcgttcg tctctgccgc cggtgatgtg 12780 tcggtggtgg atgtggcgta ctcgctgggt gtgtcgcgtg cgggtcttga gcatcgtggt 12840 gtggtggtgg gggagtcgcg tgcggagttg ctcgcggctc tggagtcgtt ggcgtccggg 12900 gttgagtcgc cgggtgtggt gacgggtcgg gtcgctgagg gtcggttggc gttcttgttc 12960 acggggcagg gtgcgcagcg ggttggtatg gggcgtgagc tggctgctgc gttcccgttg 13020 tttgcggcgt ctcttgagga gacgtgtggc ttgttggagc gtgccggggt tgcggtgcgt 13080 gaggtgctgt tcgccgagga gggttcggcc gaggccgccc tgctgacgcg gacggtgtat 13140 gcgcaggcgg cgttgtttgc ggtggaggtg gcgctgttcc ggttggtgga gtcgttcggt 13200 gtggtgccgg actttgtcgc tgggcattcg gtgggtgaga tcgctgccgc gcatgtcgcg 13260 ggggtgttct cgcttgagga tgcggtgtct ctggtggcgg ctcgtggtcg gttgatggat 13320 gcgctgccgg agggtggggc gatggtggcg gtgcaggcca ccgaggagga tgtgctcgct 13380 ctgttggagg gggtggagga tgcctccatc gcggcgatca atggccccga cgccgtggtg 13440 gtctccggca ccgaggccgg tgtcgcccgc gtagtggatg tactccggga gcggggtgcg 13500 aagaccaagc ggctcgtggt gagtcatgcc ttccactcgc cgctgatgga gccgatgttg 13560 gctgagttcg ccaccgtcgt ggaggggttg tcgttcgcgg ctcccaccat tccggtggtg 13620 tcgaatgtgt cgggtgcggt ggcggatgcc gagttgtcgt cgccgggtta ctgggtgcgg 13680 catgtgcgtg aggcggttcg tttcggtgcc ggggtggaga ccctgctcgg cgctggtgtg 13740 tcgtcgttcc tggagatcgg tccggacggt gtgctgagcg ggatggcccg cacgtccgtg 13800 cctgagggtg cggatgtgga gtgcgcgccg ctgatgcgcc ggggccgtgg tgaggtgcgg 13860 gagttcctca ccggcctctc ccggatggtc gtacggggag tcccggtcga ctggcagtcg 13920 ctggtcgagg gcggtcgcct ggccggactg ccgacgtacg ccttccagcg tgagcggttc 13980 tggctggacg ttccttccgc tgtcggtgat gtggccaccg ccggacttgc gccctcgggc 14040 caccccctgc tcggtgcggt catgcgacgc gccgatgtcg atggtgtcgt gttcacgggc 14100 cgctggtcac tgcgcagtca tccgtggctg ggtgagcacc gggtcgggtc ttcggtggtg 14160 ttcccgggga ccgggttcgt cgagctgctg atgcgcgcgg gcgacgaggt cggttgcggc 14220 cggatcgagg agttgaacca ggagactccg ctcgtcgtcc ccgagcgcgg agcgctccag 14280 ctccaggtgg tcgtgggcgc gcccgaggag accggcctcc gtggtgtcgg cgtgtactcg 14340 cgcgcggagg acgccgatgc ggatgtgccg tggacccggc acgccagtgg tctgctgagc 14400 ccggccgtgg tgccggccga cttcgagctg acgcagtggc cgccggccgg tgcggaggcc 14460 ctcaatgtcg aggacacgta ccagcgactc gctgatgccg gactggtcta cggcgagcgg 14520 ttccagggcc tcaagtcggg ctggatcaag ggtgaggaca tctacgccga gatcgcgctg 14580 cccgagcacg ccgtcgccga ggcggccgag tacacgctgc acccggcggc gctggacgct 14640 gcccttcagg cgagcggtct gaacgatccg cccgaggtgc aggcgacggc ctatgtcccc 14700 ttctcgtggt cgggggtgtc gttgtttgct tcgggtgctt cggtgttgcg ggtgtgtgtg 14760 cgtcatgtgg cgcgggatcg ggtgtcgttg ttggtggctg atggtgtggg tgtgccggtt 14820 gcggtggtgg agtcgttggt gttgcgggcg atttctgctg gtgcggtggc ggttgctggg 14880 gtgggttcgg gtgtgggtgg tgggttgttt gaggtggtgt ggtctccggt tgttggtgtg 14940 aggggtgtgg atgtgtcggg tgtggtggtg ttggaggctg gtgtgggtgt tggtggggat 15000 ggggtttcgg tggtgggtgg tgtgttggag ggtttgcagg gtgtgttggg tgggggttct 15060 ggttctcgtg tggtggtggt gacgcggggt gcggttggtt ctggtggtgt ggtggatgtg 15120 tcgggtgcgg gtgtgtgggg gttggtgcgg tcggttcagg ctgagcatcc gggtcggttg 15180 gtgttggtgg atgtgggtgt tgagggtgat gtgggtgtgg gtgtggggtt ggctttgggt 15240 tcgggtgagg agcaggtggt ggtgcgtggg ggtgaggtgt ttgttcctcg tttggcgcgg 15300 gtgggtgctg tggcggcgga tgcgggtgtt gatggtgctg agatcgcggg tggtttgggt 15360 gatggtgtgg tgttggtgac gggtggtacg ggtgggttgg gtgcgttggt ggcgcggcat 15420 gtggtggtgg agcgtggggt gcgtcgtttg gtgttggtgt cgcgtcgtgg gttgggtgct 15480 ccgggtgcgg tggggttggt ggctgagttg gagggtttgg gtgctgtggt ggaggtggtg 15540 gcgtgtgatg tgagtgatcg tgtggcgttg gcgggtgtgg tggggggtat tgggtcggat 15600 ctttcggctg tggtgcatac ggcgggtgtg gtggatgacg gtgtggtgga gtcgatgtcg 15660 gtgggtcggg tggcgtcggt gtttggtccg aaggcggatg ctgcgtggtt tttgcatgag 15720 ttgacgcgtg acatggggct gtcggcgttt gtgttgttct cgtcgatggc ggggacggtg 15780 ggtggtggtg gtcagagcaa ctatgcggcg gcgaatgctt atttggatgg tttggcggag 15840 tatcggcgtg ggttggggct ggcggcgaca tctctagcct ggggactctg ggaagagtcg 15900 acgggcatgg gcagccgcct caccgacgcc gacctggaca ggatgagccg ctcgggcatc 15960 cgtacgctct cgatcgagga cgggctggcg ctcttcgacg cggccctcgc cgccgaccgg 16020 ccgacagtca tgccggccca cttcgacatc cccgccctgc ggggacaggg cgaatccctc 16080 gcgccggtct tccgcaccct ggccggcccc ccggcccgcc gctcggcggc cgtcaccccc 16140 cgtgacatcg cggcggcgac cgagagcagc ctcaccgacc ggctcgccgg tctggacgcg 16200 gaaggacgcc gggcgctggt gctcggtgtg gttcgtgcgc aggtcgcgca ggtgctggcc 16260 tacgcctcac cggatctcgt ggagccggag cgcgccttcc aggacctcgg cttcgactcg 16320 ctgaccgccg tcgaactgcg caacggcctc acggccatcg cgggagtccg cctcccggcg 16380 acgctcgtct tcgactaccc ctcgaccgac atcctcaccg acttcctcct cgccgaactc 16440 tccgacgaga ttccggcggc ggtggcgacc ctgccggcga tgggccatgt cgtcgacgac 16500 gacccgatcg ccgtcatcgg catgggctgc cgctaccccg gcggggtcga gtcccccgag 16560 gaactgtgga agctcatggc ggagggccgg gacgccatct ccgagttccc gaccgaccgc 16620 gggtgggacc tcgatgccat ctaccacccc gacccgatgc acacgggcac cagctacacc 16680 cgcgagggtg gcttcatcca caacgcgggc gacttcgacg ccgccttctt cgggatctcg 16740 ccgcgcgagg cgatggagac cgacccccag cagcgactgc tccttgagac gtcctgggag 16800 gcgttcgagc aggccgggat cgtccccacc gatctcaagg gcactcagac cggtgtcttc 16860 gccggtgtca tgtaccacga ctacgcgggc aacatcggct ccggcagcat cgtcacgggc 16920 cgcgtcgcgt acaccctggg cctggagggt ccggcagtct ccatcgacac cgcctgctcg 16980 tcgtccctgg tcgccatcca cctcgccgcg cagtccctgc gtcagggcga gtgctccatg 17040 gccatcgccg gaggtgtcgc cgtcatggcg acgccggagt cgttcatcga attcagccgc 17100 cagcgcgcgc tctcccagaa cggccgctgc cgcgccttct cctcggacgc ggacggtacg 17160 gcctggggcg agggtgtcgg tgtcctgatc ctggagcggt tgtcggacgc gcggaagaac 17220 gggcacgagg tactcgcggt catccgtggt tcggcgttga accaggatgg tgcgagcaat 17280 ggtctgacgg cgccgaacgg tccgtcccag cagcgggtga tccgccaggc gctggcgaac 17340 tcgggtctgt cggccgccga ggtggacgcg gtcgaggcgc acggcaccgg taccacgctc 17400 ggtgacccga tcgaggcgca ggcactgctg gcgacctacg gcaaggagcg ggacgcggac 17460 cagcccctct ggctcggttc gtccaagtcg aacttcggtc acaccaaggc cgccgccggt 17520 gtcgccggtg tgatcaagat ggtgatggcc atcaggaacg gtgtgctgcc gaagacgctg 17580 catgtcaccg agccgtcgcc gcacgtggat tggtctgctg gtgcggtgga gctgttggcg 17640 gaggctcggg agtggcctga gacgggtcgt ccgcgccgcg ccggtgtgtc gtccttcggt 17700 atcagtggga cgaacgcgca cgtgatcgtg gagcaggccc ccaccgacca ggccgctacc 17760 aagccgaagg ctgccgacgc ggtcccgggc ctgcccgttc cgtgggtggt gtctgcgaag 17820 aacccggagg cgttgcgggc gcaggcgggt cggttggggt cgttcttggg tgagaccggt 17880 gttgttgatg tgccggcggt gggttggtcg ttggtgcggg gtcgttcggt gttcgcgcat 17940 cgggcggttg tggtgggtgg tgagtgggac gcgctgctgg cgagtatcgg tgaactggcc 18000 gatggcgccg aggatggttc cggtgctgcc tctggttctg ttgtgtcggg tgtggcggat 18060 gtgtcggggc gtcgggtgtt tgtgttcccg gggcagggtt cgcagtgggt tggtatggcg 18120 caggggttgt tggattcgtc ggtggtgttc acggagcgga tgacggagtg tgctgcggcg 18180 ttggatccgt tggtggagtg gtcgttgttg gatgtggtgc ggggtgtgga gggtgcggcg 18240 tcgttggagc gggtggatgt ggtgcagccg gtgttgtggg cggtgatggt gtcgttggcg 18300 tcggtgtggc gttcggtggg tgtggtgccg gatgcggtgg tgggtcattc gcagggtgag 18360 atcgcggctg ctgtggtggg tggttggttg tcgttggtgg atggtgcgcg ggtggtggcg 18420 ttgcggtcgt tggcgattcg tgaggtgttg gcgggtggtg gtggcatggt cgcggtccag 18480 gctgcggagg atgaggttgc tgggtggctt gagggtgtgg agggggtggg gattgctgcg 18540 gtgaatggtc cgcgttcggt ggtgatctcg ggtacgcgtg cgggtttgga tgcgtgtgtg 18600 gagttgtggt ctgggcgggg gacgtgggtg aagcgggttc cggtggacta tgcctcgcat 18660 tcggctgagg tggagcgggt gcgtgagcgg gtgctggcgg atctggcgag tgtgacgggt 18720 ttgtcggggt cggtgccgat gttgtcgacg atgacgggtg actggattgt tgagggtcag 18780 gttggggccg ggtattgggt ggagaatctg cgtcgtccgg tgttgttcgc ggacgcgacg 18840 aggcggttgg cgtcggaggg tttcggcgcg ttcgttgagg tgagtgcgca tccggtcctg 18900 gtcatgggca tcgaggagac cttggaggcc catcacaccg ccacgaccga cgacgacacc 18960 accacccgaa cccccgtggt caccgtcggc acgttgcgtc gtggtgaggg tggttgggat 19020 cagttcctgc gctccctcgc ggggctcttc gtccggggtg cggtgacacc ggattgggag 19080 tcgttgctgg gcggtacgcg tccccgggtc gacctcccga cctacgcctt ccagcgtcgg 19140 cgcttctgga tcgagagcgt caggaaggaa gcggtgacac tcgccgccga cccggtcgac 19200 gccgcgttct gggaggccgt cgagagcgcc gacctggcga agctcgccga cagcctgcgc 19260 atcgagaccg acgtactcga aggcgtactc cccgcgctca cctcctggcg gacacgcagc 19320 cgtgagcagt cgctcgtcga cggctggcgc taccgcgagg agtggaagcc ggtgcccgca 19380 ccgaccccga acagcgccac cggcacctgg accgtgctgg tcccggccac ccaccagggc 19440 gacgccaccg tgaccggtgt gctggacggc ctgcgccgtg gcggcgccga catccgggtg 19500 ctcgaggtca ccgccaccga ccgcgaggcc ctggccgagc agctccgcgc cgaactcgcc 19560 cagagcgagc cccggctcat cctctccctg ctggcactgg acgaccgcgc ccacccccgt 19620 caccccgagc tgaccgaggg catcaccgcc accatcgctc tcgtccaggc gctggacgac 19680 tgcggcgcca ccgcccggct ctggtgcgcc acctcgctgg ccgtcgcggt caccgaatcg 19740 gccgaggtgc tcaaccccgt acagacgacc gcctggggca tgggcgcgtc cttcgcgctc 19800 gaccaccccg agacctgggg cggactggtc gacctcccgg ccgacatcga cacccgtacc 19860 gcggacatcc tctgctcggt cctggcgtcg gacctccagg aagaccagat cgccctgcgt 19920 acggccggcc tcttcgcccg ccgtatggtc cgggcccgcc tcgacgaatc cgccgtggcg 19980 acagagcagc cgtggcggcc caacggcacc gtcctggtca ccggaggcac cggcgggatc 20040 ggctcgcacg tggcgcgctg gctggcggcc gccggtgcgg agcacctcgt actcaccagc 20100 cgtcgcggtg ccgaggcgcc cggcgccgcc gaactcgaag ccgagctggc cctgctgggt 20160 gccaaggtga ccctcgccgc ctgtgacatg ggagaccgcg agtccgtacg ggaactcgtc 20220 gccgccctcc ccgacgccgc accgctcacg gccgtcttcc acctggccgg cgcactcccg 20280 gacggcgagc gccgactctc ggcgacgacg ttcgaggact tctcccggat gacccgggcg 20340 aagatcggtg gagccgttca cctggacgag ctgctcgcgg accgcgagct cgcggccttc 20400 gtgaccttct cctccggctc ggcgatctgg ggcaacgcca accaggcggc gtacggcgcg 20460 tccaacgcgt tcctcgacgg cctcgtccac aaccggcggg cacgtgggct cgccgggacg 20520 tcgatcgcgt gggggctctg gggcggtgac ggcacggaca ccgagaccga cgagcagctc 20580 agccgcatcg gtgtcaggtc gatggaccct cggctggccc ttgaggtcct ccggcaggcc 20640 ctcgaccagg acaccagcca tctgatcgcc accgacatcg actggcagcg cttcgccccg 20700 gtgttcacca tcgcccggcc gcgcccgctg ctggacggaa tcgccgaggt cagggccgtc 20760 ctgtcggcgg acaccgccga ggtcgggccg gccgacgatg acaccccgaa ggagaccgtc 20820 gtcacccggc tcgccggcct cagccccgcc gagcgtgacc acgccctgct ggagctcgta 20880 cggacacagg tggccgcggt gctccgctac tcggacacct cggacgtcga gcaggaccag 20940 tccttcaagg acctcggctt cgactccgtc accgcggtcg aactgcggaa caagctcaca 21000 cgcggcgtcc gcgctgcggc tgcccgccac ggcgtcttcg actacgccac cccggtcgcc 21060 ctcgcggccc atctgcggtc ggagctgttc acggacgacg ccgcggcgtc gggagaggtg 21120 ccgctgctgg cggagctcga ccggatcgag gcggcggtga cctcgctccc gtcggccgac 21180 atcgagcgga tgcacctcac ctccaggctt cagagcctgg tgaccaagtt gaacgacatc 21240 gtcggcgcgg gagctcccct ggaagcggag gccatcgcgg acaagctcga aacggccact 21300 gccgatgaca tcttcgcgtt catcgacaag gacctcggtc tgaactgacc ggcacgtccc 21360 cgcctccccg cgctcccgct ccctcgcaca aagattggtg tgtcaccgga atgtcgaacg 21420 aagagaagct cctcgactac ctcaagcggg tcaccgccga tctccacgcg acccggcagc 21480 ggctgcgtga ggcggagtcc gatgagcagg agccgatcgc ggtcgtcgcg atgggctgcc 21540 gctacccggg ggacgtccgt acccccgagg acctgtggca gctcgtcgcg acgggcggtg 21600 acgccgtcac cgaattcccc gccgaccggg gctgggactt cgacacactc ctcggcggcg 21660 atgcgggcgc atccgggagc acctatgtgg cccgcggcgg gttcgtccac gacgcggccg 21720 acttcgatgc ggacttcttc ggcatctcgc cgcgcgaggc gctggcgatg gacccgcagc 21780 agcggctgct gctggaactc gcctgggaga ccagcgagcg ggccggcatc gacccgcaca 21840 gcctgcgggg tgcctccgtc ggcgtcttcg ccggcaccaa cggtcaggac tacgccgacc 21900 tgatggaccg ggcgccggag gacaccgagg catacctctc caccggtagc gtcgcggccg 21960 tcgtctccgg ccgggtctcg tacgcgctgg gtctggaggg cccttcggtc tcggtcgaca 22020 ccgcctgctc ctcctcgctc gtcgcgctgc acctcgcctg ccaggcactc cggcagaagg 22080 agtgctccat ggccttcgcg ggtggcgtca cgatcatgtc gacgcccggg ccgttcatcg 22140 ccttcagcag gcagagcggt ctcgcgtcgg acggccggtg caaggcgttc tccgacgaca 22200 cggacggtac ggggtggggt gagggcgcgg gcctcctgct gctggagcgg ctctcggacg 22260 cgcgcaggaa cgggcatcag gtgctcgccg tggtgcgggg ctcggcgttg aaccaggatg 22320 gtgcgagcaa tggtctgacg gcgccgaacg gtccgtccca gcagcgggtg atccgccagg 22380 cgctggccaa cgccggtctg acggcggccg aggtggacgc ggtcgaggcg cacggcaccg 22440 gtacgaccct cggtgacccg atcgaggcgc aggccatcct cgccacgtat gggcagagcc 22500 gcgagcagga ccagccgctc tggctcggct ccatcaagtc gaacatcggt catacccagg 22560 ccgcggccgg ggtcagcggt gtgatcaaga tggtgatggc catccagaac ggcgtgctgc 22620 cgaagacgct gcatgtgtcg gagccgtcgt ccgttgtgga ttggtccgct ggtgcggtgg 22680 agctactcac ggaggctcgg gagtggccgg agaccggtcg tccgcgccgt gccggtgtgt 22740 cgtcgttcgg tgtgagcggt acgaacgccc acatcatcat ggagcaggcg cccgtgcctg 22800 aggcagagtc ggagccggac ggcgaagcac ccgccgcggt gtccgggctg ccggttcctt 22860 gggtggtctc cgggaagacc gccgacgcgt tgcgggcgca ggccgagcgg ctgctgtcgt 22920 tcgtctccgc cgacgcggat gtctccgtgg tggatgtggc gtactcgctg ggtgtgtcgc 22980 gtgcgggtct tgagcatcgt ggtgtggtgg tgggggagtc gcgtgcggag ttgctcgcgg 23040 ctctggagtc gttggcgtcc ggggttgagt cgccgggtgt ggtgacgggt cgggtcgccg 23100 agggtcggtt ggcgttcttg ttcacggggc agggtgcgca gcgggttggt atggggcgtg 23160 agctggctgc tgcgttcccg gtgtttgcgg cgtctcttga ggagacgtgt ggcttgttgg 23220 agcgtgccgg ggttgcggtg cgtgaggtgc tgttcgccga ggagggttcg gccgaggccg 23280 ccctgctgac gcggacggtg tatgcgcagg cggcgttgtt tgcggtggag gtggcgctgt 23340 tccggttggt ggagtcgttc ggtgtggtgc cggactttgt cgctgggcat tcggtgggtg 23400 agatcgctgc cgcgcatgtc gcgggggtgt tctcgcttga ggatgcggtg tctctggtgg 23460 cggctcgtgg tcggttgatg gatgcgctgc cggagggtgg ggcgatggtg gcggtgcagg 23520 ccaccgagga ggatgtgctc gctctgttgg agggggtgga ggatgcctcc atcgcggcga 23580 tcaatggccc cgacgccgtg gtggtctccg gcaccgaggc cggtgtcgcc cgcgtagtgg 23640 acgtactccg ggagcggggt gcgaagacca agcggctcga cgtcagccac gccttccact 23700 cgccgctgat ggagccgatg ttggctgagt tcgccaccgt cgtggagggg ttgtcgttcg 23760 cggctcccac cattccggtg gtgtcgaatg tgtcgggtgc ggtggcggat gccgagttgt 23820 cgtcgccggg ttactgggtg cggcatgtgc gtgaggcggt tcgtttcggt gccggggtgg 23880 agaccctgct cggcgctggt gtgtcgtcgt tcctggagat cggtccggac ggtgtgctga 23940 gcgggatggc ccgtgggtcg atctccgacg gcgccgacgt tggctgtgtc cccgtgatgc 24000 gccggggccg gggtgaggtg cgggagttcc tcaccggcct ctcccggatc gccgtacggg 24060 gagtccccgt gagctggggt ccgctgctgg cgggtggtcg gcgggtcgag ctgccgacgt 24120 acgccttcca gcgtcgccgg ttctggctgg aggcggggca ctccgtcacg gacgcttcgg 24180 gtctgggcca gacggctgcc gggcatccgc tgatcggtgc tgtggtgagt ctggccggtg 24240 gtgacggtgc cgtgctgacc ggtcgggtgt cgttgaacac gcatccctgg ctgggcgacc 24300 accgggtcgc gtcttcggtg gtgttcccgg ggaccgggtt cgtcgagctg ctgatgcgcg 24360 cgggcgacga ggtcggctgc ggccggctgg aggagctgaa ccaggaggca ccgctcgtcg 24420 tacccgaccg gggcgccgtc cagatccagg tgaccgtgga ggcccccaat gctgtgggag 24480 agcgaccggt cgcggtttac tcgcggctgg aggacacgga tacggacgcc ccgtggaccc 24540 ggcacgccag tggtctgctg agcccaacca ccgcttcggc ggacttcgac ttcacggcat 24600 ggccgccggc cggtgcggac cccctctccg tcgacggaat gtatgaccgc ccggactcgg 24660 gcctggtcta cggtcccctg ttccaggggc tgacggccgc ctggcgcaag ggcgatgagg 24720 tgtacgcgga gatcgagctg cccgaggggg cggcggtcga cgccgcccgc ttcgggatgc 24780 accccgccct cctcgacgcc gccctccacg ccctcgggtt ctcggcctcc tacgaggacc 24840 aggaggagga cggcaccgtg gcccggctgc ccttctcgtg gtcgggggtg tcgttgtttg 24900 cttcgggtgc ttcggtgttg cgggtgtgtg tgcgtcatgt ggcgcgggat cgggtgtcgt 24960 tgttggtggc tgatggtgtg ggtgtgccgg ttgcggtggt ggagtcgttg gtgttgcggg 25020 cgatttctgc tggtgcggtg gcggttgctg gggtgggttc gggtgtgggt ggtgggttgt 25080 ttgaggtggt gtggtctccg gttgttggtg tgaggggtgt ggatgtgtcg ggtgtggtgg 25140 tgttggaggc tggtgtgggt gttggtgggg atggggtttc ggtggtgggt ggtgtgttgg 25200 agggtttgca gggtgtgttg ggtgggggtt ctggttctcg tgtggtggtg gtgacgcggg 25260 gtgcggttgg ttctggtggt gtggtggatg tgtcgggtgc gggtgtgtgg gggttggtgc 25320 ggtcggttca ggccgagcat ccgggtcggt tggtgttggt ggatgtgggt gttgagggtg 25380 atgtgggtgt gggtgtgggg ttggctttgg gttcgggtga ggagcaggtg gtggtgcgtg 25440 ggggtgaggt gtttgttcct cgtttggcgc gggtgagtgt tgtggcggcg gatgtggtgc 25500 cggatgcggg tgttgatggt gccgatatca ggggtggttt gggtgatggt gtggtgttgg 25560 tgacgggtgg tacgggtggg ttgggtgcgt tggtggcgcg gcatgtggtg gtggagcgtg 25620 gggtgcgtcg tttggtgttg gtgtcgcgtc gtgggttggg tgctccgggt gcggtggggt 25680 tggtggctga gcttgagagc ttgggtgctg tggtggaggt ggtggcgtgt gatgtgagtg 25740 atcgtgtggc gttggcgggt gtggtggggg gtattgggtc ggatctttcg gctgtggtgc 25800 atacggcggg tgtggtggat gacggtgtgg tggagtcgat gtcggtgggt cgggtggcgt 25860 cggtgtttgg tccgaaggcg gatgctgcgt ggtttttgca tgagttgacg cgtgacatgg 25920 ggctgtcggc gtttgtgttg ttctcgtcga tggcggggac ggtgggtggt ggtggtcaga 25980 gcaactatgc ggcggcgaat gcttatttgg atggtttggc ggagtatcgg cgtgggttgg 26040 ggctggcggc gacatccctg gcctggggac tctgggaaga caccgcgaac ggcggtatga 26100 cgggccacct ggccgaagcc gaccgtacgc ggatggcacg cgggggagtc ttccctctgg 26160 cgctggacga ggggctcgca ctcttcgacg ccgccctcgc caccggaaag gcgacactcg 26220 tccccgtcca tctggacacc accgcgctgc gcgcacacgc tgacgaactg cccgccctct 26280 tccgtgacct cgtccgcgcg ccgaagcggc gcacggcggc ggaaggccgt gcggcggact 26340 ccgccgacga cctcgcgggc cgcctcgccg gcctggccgc cgaggcgcgc cggccgttgg 26400 tgctcggtgt ggttcgtgcg caggtcgcgc aggtgctggg gtacgcctcg gcggatctcg 26460 tggagccgga gcgcgcgttc caggacctcg gcttcgattc gctgacggcc gtcgaactgc 26520 gcaacggcct cacggccgtc gcgggggtcc gcctcccggc gacgctcgtc ttcgactatc 26580 cctcgaccga catcctcacc gacttcctcc tcgccgaact ctccggcaag gtcgccgtgg 26640 ccgcgcccct cgcgccgctc gccaccaccg ggccggtgca cgacgacccg atcgtcgtca 26700 tcggcatggg ctgccgctac ccaggcgggg tccgctcgcc ggaggacctg tggcggctgg 26760 tcgccgatgg ccgggatgcg atatcggagt tcccgaccga ccgcggctgg gacctcgacg 26820 cgctgtacca cccggacccg gaccacgccg ggaccagcta cacccgcgag ggcgggttcc 26880 tgcacgacgc ggccgatttc gacgcggact tcttcgggat ctcgccgcgt gaggccatcg 26940 tcatggaccc gcagcagcgg ctgctccttg agacgtcctg ggaggcgttc gagcaggccg 27000 gcatcgtgcc cgccgacctc aagggcaccc agaccggcgt cttcgccgga gtgatgtacc 27060 acgactacgg cacccgaatc gtcgacattc ccgagggggc cgaaggctat ctgggcaccg 27120 gcatctccgg cagcgtcgtc tccggccggg tcgcgtacac cctgggtctg gagggcccgg 27180 cggtcacgat cgacaccgcc tgctcctcct cgctcgtcgc cctgcattcc gccgcgcacg 27240 ccctgcgcca gggtgagtgc tccatggcca tcgccggtgg tgtcaccgtc atggcgggcc 27300 ccgacacctt catcgacttc agcaggcagc gcggtctggc cacgaacggt cgctgcaagg 27360 cgttctcggc ggacgccgac ggcaccggct ggggcgaggg cgtcggcgtc ctggtcctgg 27420 agcggttgtc ggacgcgcgg aagaacgggc acgaggtact cgcggtcatc cgtggttcgg 27480 cgctgaacca ggacggtgcg agtaacggtc tgacggcgcc gaacggtcct tcgcagcagc 27540 gggtgatccg ccaggcactg gccagcgccg gtctgacgac gtcggacgtc gacgcggtcg 27600 aggcgcacgg caccggcacc acgctcggtg acccgatcga ggcccaggcg gtgctggcca 27660 cctacggcca ggatcgcgcc gcggaccagc cgctctggct cggctcggcc aagtcgaact 27720 tcggtcacac gcaggccgcg gccggtgtcg ccggtgtgat caagatggtg atggccatcc 27780 ggaacggcgt gctgccgaag acgctgcatg tgtcggagcc ttcgacacat gtggactggt 27840 ccgccggcgc cgtggagctg ctggcggagg cccgggagtg gccggagacc ggtcgtccgc 27900 gccgcgccgg tgtgtcgtcg ttcggtgtga gcggtacgaa cgcgcacgtc atcgtcgagc 27960 aggcccccac cgaggagcag gcccccgcgg acgcgcctgc cccgacggac gcgcccgccg 28020 gcactccggt gccctggatc gtctccggtc ggaccgccga ctcactgcgc gaccaggccc 28080 gccgtctgct ggagcacctc gaccggaacg gcgacctcga cccgcaggac gtcgcgcggg 28140 ccctcctcac cacccgtacc cgcttccacc accgtgccgc cgttgtggcg accgagcgac 28200 aggacatcgt cgcggcgctc gaagcactcg ccgacggccg gcccgtgagc ggtctggttc 28260 aggggacggc caccaccatg gcgaagtccg cgttcctgtt cacggggcag ggtgcgcagc 28320 gggtcggcat gggtcgggaa ctcgcggccg aattcccggt gtttgcggcg tctcttgagc 28380 agacgtgtgg tctgttggag cgtgccgggg ttgcggtgcg tgaggtgttg ttcgccgagg 28440 agggttcggc cgaggccgcc ctgctgacgc ggacggtgta tgcgcaggct gcgttgttcg 28500 ccgtcgaggt ggcgctgttc cggttggtgg agtcgttcgg tgtggtgccg gactttgtcg 28560 ctgggcattc ggtgggtgag atcgctgccg cgcatgtcgc gggggtgttc tcgcttgagg 28620 atgcggtgtc cctggtggcg gctcgtggtc ggttgatgga tgcgctgccg gagggtgggg 28680 cgatggtggc ggtgcaggcc accgaggagg atgtgcttgc cctcctggag ggggtggagg 28740 acgcctccat cgccgcgatc aacggccccg acgccgtggt cgtctccggc accgagaccg 28800 gtgtcgcccg cgtagtggac gtactccggg agcggggcgc gaagaccaag cggctcgacg 28860 tcagccacgc cttccactca ccgctgatgg agccgatgct cgccgacttc gcacgggtgg 28920 tcgcgggtct gtcctatgag gaccctgcga tcccggtcgt gtcgaatgtg tcggggtcga 28980 tggcggacgg tgagctgtcg acgccgggat actgggtgcg gcatgttcgt gaggcggttc 29040 gtttcggtgc cggggtggag accctgctcg gcgctggtgt gtcgtcgttc ctggagatcg 29100 gccccgatgg tgtgctgagc gggatggccc gtacgtccgt acctgagggt gcggatgtgg 29160 agtgcgcgcc gctgatgcgc cgagaccgcg ccgaggtacg ggagttcctc accggcctct 29220 cccgtctcgc cgtacgcggt gtcccggtga gctggtcccc cctcgtggcg gggggccggc 29280 gggtcgagct gccgacgtac gccttccagc gtcgccggtt ctggctcgac gccggacact 29340 cggtcacgga cgcttcgggt ctgggccaga cggccgccgg gcatccgctg atcggtgccg 29400 tggtgggtct ggccggtggc gatggtgtcg tcctgaccgg tcgggtgtcg ttgcacaccc 29460 acccctggtt ggcggatcac caggtcgcgg gggtgacgct gcttccgggt acgggctttg 29520 tggagctggc ggtccgtgcc ggtgacgagg tcggctgtgg ccggctggag gaactgaccc 29580 tggaggcccc gctggtcgtg cccgaccggg gcgccgtcca gctccaggtc gtcgtcggcg 29640 ggctggagga atccggcgtc cgtaccgtca gcgtctactc ccgagccgag gacaccgaca 29700 accccgacac cccctggacc cggcacgcca gtggtgccct cggcacggcg gccgacccgg 29760 ccgacttcga cctcaccgcc tggccgccgg ccggaaccga ggccgtcgag atcggggact 29820 tctacggcga actggccgcc acacccgacg gtctggtcta cggtccgctg ttccaggggc 29880 tgacggccgc ctggcgcaag ggcgatgagg tgtacgcgga gatcgagctg cccgagggcg 29940 cggcggtcga cgccgcccgc ttcgggatgc accccgccct cctcgacgcc gccctccacg 30000 ccgtcggact ctcgaacgac gccgacgccg acgccgacgc gggcacggca caggaggacg 30060 gcaccgtggc ccggctcccc ttcgcctggt ccggtgtgac gctccaccgc tccggcgcga 30120 cccggctgcg gctctccgta cggcccaccg gaggcgacag ctaccacctg cggatcgccg 30180 acgcggtcgg cgcgcccgtc gcgaccgtcg gggaactgct gctgcgcggt atcagcgccg 30240 agcagctcgc gcgggccggc accgaccgcc cggacgcgct cttccggctg gagtgggagg 30300 cgctgcgcgg cgacggggcg accaccgcgg gggagtgggc gctgctcgga ggggacccgt 30360 acggtctcgc tccggcccgt gccgtcccgt acggcgatct cgacgccctg gcggccgagg 30420 ccgagggcgg cacgccgccc gaggtcgtcc tgctgcccct gacagtgccc gccggcgaag 30480 agccggacgc gggcgagcgg gccgcgcacc gggcgctgcg cgcggtgcgg tcctggctcg 30540 ccgacgaccg gttcgcggct gcgaccctcg tcctgatgac caggggcgcg ctggcggcga 30600 cccccggcga tgaggtcacc gatgtggcgg gcgccgaggt ctggggcctc gtacggtcgg 30660 cgcagaccga gcaccccggc cggttcgtcc tggtcgactc ggacggttcc gaggcgtccg 30720 cgcgggcgct cccggccgcc gtggcgagcg gtgagccaca gctcgcactg cgcgcgggta 30780 ccgtcaacgc ggcccggctg ggccgcgtgg agcgggccgg ggcggaggcc gtggccacgt 30840 tcgatcccga gcggaccgtc ctgatcaccg ggggtacggg cgcgctcgcc ggccaactcg 30900 cccggcatct cgcccgtgcg tacggcgtcc ggcatctgct gctcgccggg cggcgcggcc 30960 cgagcgcccc ccacgcggcg gagctggtcg ccgagctggc cgaactgggc gccctggccg 31020 aggtcgtggc ctgcgatgtg gccgaccgtg aggcgctgac cgccctgctg gccgcggtcc 31080 ccgccgaccg gccgctgggt gccgtcgtgc acacggcggg ggtcctggac gacgggctcg 31140 tggagtccct cacgcccgag cggctcgacg cggtgctcca cccgaaggcg accgcggccc 31200 tcctgctcga cgaactgacc cgtgacgccg acctgacggc gttcgtgctc ttctcctccg 31260 ccgcgggcac cctcggcagc cccggtcagg ccaactacgc ggcggccaac gccggtctcg 31320 acgcgctcgc cgtccggcga cgcggccagg ggctgcccgg tctgtcgctc ggctggggcc 31380 tgtggcaggc ggacggcggt atgggcggcg cgctcagcgg cggcgaccag gcgcgtatcg 31440 cccgtggtgg tgtcgccgcg ctcacgaccg accacggtct ggcgctcttc gacaccgcct 31500 gcgccggtcc ggacgccgtc gtactgccga tgctgctgga cctgcgaccg caggacgacg 31560 taccgcatct gctgcggtcc ctggtgagcg cgcgccgcaa gggcgcgtcg gcgggagccc 31620 gccacgaggg tccggccgag ctgcggcgca ggctcgccgc cgcgacgccc gacgagcggt 31680 acgaacacct cctcggcctg gtccgctcgt gcaccgccgt ggtgctgggg caccggggcc 31740 cgcaggacgt cgatcccggg gtcgggttcc tggagtccgg tttcgactcg ctgaccgcga 31800 tggagctgcg caaccagctc aacgaggcca ccggtctgcg gctcgcggcc accgtcgtct 31860 tcgaccacac cacccccgca gatctggcgc ggcacctggt cgacggagtg gccgacacgg 31920 tcgccgccgc accgggccag cagccggcgc cgcggtcgga cgacgacgcg gacaccctga 31980 gcgggctgtt ccgtacggcg gtacgggccg gtcaggtgac gaagggcgtc gatctgctac 32040 gggccgtggc cgagctgcgc ccggccttcc acagcgccga cgaactgggc gacgatctgc 32100 cggtgccggt acggctcgcc cagggcccga gtgccgcgcg gctgttctgc ttcgcctcgc 32160 cgatggcgat gggcggcacg caccagtacg ccaggctggc ggcgcacttc cggggcgtac 32220 gcgaggtctc ggcgctcccc atgcccggat tcgcgacggg agacctgctg ccggcgacgg 32280 ccgaagccgt cgtggaggtc ttcggccgga gcctcctgcg ggcggccggg gacgagccgt 32340 tcgtcctcct cggctactcg gctggcggtg tcttcgccca cgcggtggcc gcctggctgg 32400 agtccgaagg gtgcgcgcca gccgccgtgg tgctgctgga cagctaccgc gcggacggtg 32460 gcaccagcat ggacggcgac ttctgggtga gcatggtgga gggcctgttc tcgcgggaag 32520 aggtcttcgg acggttcacc agcgcccgac tgtcggcgat gggccggtac gcgcggctcg 32580 tcggcgaggt caagacgggt gaggtgaagg cgccggtgct cttcgtccgc ccggagcggt 32640 cgctgagcgc gagcgccgac gcgggcggag tcgggggcgg ggacgccggg gccgctgccg 32700 ccacggatga ctggcgggcc tcgtgggaca cggccgagac ggtgctggag gtggcgggcg 32760 accacttcga catcatcgag agccaggccg ccgcgaccgc cgacgccgtg gagggatggc 32820 tcgcggaccg ggtctgaccc gtctccccat cagccggtcg agcgccggag gacatcgctg 32880 agggccgacc ccgcacaggg gccggccctc ggccgtaggt acgggtggga cgcgtacccg 32940 ccgtccgcat cgcgtgcctt gctcgtaccg cgacctgctc gtaccgcgac ctgctcgtac 33000 cgtgacccct gcctgtacgc gccctgcccg cactgcgatc ctgcccgcac tgcgatcctg 33060 cccgcactgc gatcctgccc gtacgcgccg tgcccgtacg ccccctgccc ataccgcact 33120 tgtccgtacg cgccccgcct cccgtacgag cgcgcgcggg aacagcattc ccgtacgacg 33180 tcaggggcgg tgcggcgagg atcccggccc ggaagccgtt gtccttgccg caccgcccct 33240 gacggtgcgg agcgcgtcag cctatggctg tcgcaccccc acgaagacac cgcggtcgac 33300 atacccgtcg ggcaggtact ccaccgagca cccggccgcg cggaacgcct cctcgtactc 33360 gtccttggag aacagcgaca gctcctgttc gtccacgaag tgccgtacgg gatcgtcgcc 33420 gctcgtcacc aggtagtgca tctccacatg gctgcgcccg gcccgggtgg tccagcggcc 33480 catgcggacc accttgccgc cctcgttctc gaagctcgcc tccaccagat cgccgccgtt 33540 ccaactgtcc cgcagaatcc acggctcgat gatcagcacc ccgccgggac gcagatggtg 33600 ggccatgttc ttcagggcgg cgaacagacc gtccagggtc tccagatagc cgacggagct 33660 gtacatcgaa cagatcacgt cgaagctccg gtcgagcccg aaggtgcgca tatcgccctc 33720 gtggaccggc acccccggca gcttggcctc ggcgacccgg accatcggcg ccgacaggtc 33780 cacaccggtg acggcgaaat cgtccctcag cagcgcgagg tgctcgccgg tgccacagcc 33840 cacatcgagc agatcggccg ctccggggtt gcgttcgagc gccagctcgc ggatgcgggc 33900 ggcctcaccg gcgtagtcct tgtgccgccg atagatgtcg tcatagacgc gcgcgaagtc 33960 ctcttcgtac atgaaggagt cacctggccg gggttcgggc actgacacag cgccggatga 34020 tgtcgcagac ctgatcgatc tccgacggcc cgacggtggt acccgtcggg agggcgagca 34080 cgcgctcggc cagtgcctcc gcgtgcggca gagggtgtgg cgcgtgccgg gcggggtcgc 34140 tcagataggg ctccacctga tggcaactgg ggtggaagta gcggcgcgag aggacgttct 34200 gggcgatgag ggcggtgtgc acctcgtcgc ggtggatacc cgccactgcg gcgtcgatct 34260 cgatcaccag atactggtgg ttggcgcgct cgccctcggc ctgaccgcgt acccagacac 34320 cgggcagccc gtccaggccc ttctcgtagc ggccgtggtt gatccggttg gcctccatga 34380 ggctgtccat cacctccagc gaggtgagac ccatggccgc cgctgcttcg ttcatcttgg 34440 cgttggtccc gccggagcgg atctcaccgg cgctggtgat gccgaagttg cgcagctcgc 34500 ggcagcgctc ggcgaactcg gcgtcccggg tgacgatcgc gccgccctcg aagctgttga 34560 cgaacttggt cgcgtggaag ctgtacacct ccgccgtgcc gaagccgccg acggggcggc 34620 ccttgtaggt gcagccgatg gcgtgcgcgg agtcgaacag cagcggcagt ccgtgccggc 34680 cggcgatctc ctccagctcg tccacctcgc aggggcggcc gaagacgtgc acgcccatga 34740 tgccgcgggt gcgcgggccg atcagcgcct cgaccttggt ccagtcgatg tttccggtcg 34800 tctcgtcggc gtcgcagaag acggggacga ttccgatcca gtccagtgcc gccgcggtgg 34860 ccacccaggt gaaggccggg acgatgacct cgtcgccacc ccggattccc gcggccttcg 34920 ccgccacctg gagcccgatc gtggcgttgc acaccgcgac gcagtggtcg acaccggcga 34980 cctcggcgag tctctcctcg aattctcgga ccagcggacc attggtgaga tagagccggt 35040 cgagtgctcc ctccagtctc tccgtcaggc gggcacgact gcctatattg ggtcgcccga 35100 catgcaacgg ctcgcggaac acaggggaat cagtcacctg ttcatcgttc cgttcacccg 35160 cccctagcct caacctgcgg gcatgggcgc gccccagtag gggccgccgc cagcccctaa 35220 ccacccccct atgcggtccc actgctgctg acgcggcggc ctccgcggca ctagcgtcgg 35280 cgccgtctgc cactgagttc accatggcca gccgccccaa tggagatttc catgaccgag 35340 acgctgtcga ctcttccgcc cacccacacc ggcgacgagt cgctcgcggt ccgtatcgcc 35400 aagtcggtga gtgtcgtcga cgacggggcg ctgcacagcc tcgacgaatt ccacgactgg 35460 ttcaccgcca gagggcagcg gaccgcacat gtcgagagag tgccgctcga cgaactcact 35520 ggttggagct ccgatcccgt gaccgggaac atcgggcacg acagtgggaa gttcttcagt 35580 gtgcaggggc tctccgtcga actgcccggt gcgccggtgc ccgcctgggc gcagcccatc 35640 atcaatcagc ccgagatcgg gatcctgggg attctgatca aggaattcaa cggtgttctg 35700 cactgtctga tgcaggcgaa gctggagccg gggaaccgca acggcctcca gctctccccg 35760 acggtgcagg cgacccggag caactacacc cgggtgcacc agggcaaccc cgtcccgtac 35820 gtgggctact tccaggacac ctcggcgaac cgggtgatca ccgacgcgct ccagtccgaa 35880 cagggctcgt ggttctacca gaagcgcaac cggaacatgg tcgtcgagac cgaggcggag 35940 atcgagcagc acgaggcgtt catgtggctg accatcggtc agctgcaccg cctccttgcg 36000 atcgacgacc tgatcaacat ggacacccgt acggtgctgt cgtgtctgcc cttctccggt 36060 gcgcagctcg ccgagcagct cccgggcacc ggcggcgatc tgcggatgcc gatcctgcgc 36120 tcgtgcagcg aggaccaggg cagtctgcac accaccgggg acctgctgag ctggatcact 36180 gacgcccgta cccgcaacga ggtgcgcacc cggctgacgc cgctgcgcga cgtggcgggc 36240 tggcggcgca ccccggacgc gatcacgcac gacacgggtc ggttcttcga cgtgatggcc 36300 gtgcgcatcg agaccgacgg ggaccgcgag gtccgccagt ggacccagcc gatgatcgcg 36360 ccggccggga tcggcatcgt ggcgttcctg gtcaagcgga tcgacggggt gctgcacgtg 36420 ctggcgcacg cccgggtcga gccgggctat ctcgatgtcg tggagctgtc gcccacggtc 36480 atgtgcacgc ccggcaacta cgagggcctg cccgccgccg cccggccgcc gttcctcggc 36540 gaggtgctct cggcccgtcc cgagcaggtc cgcttcgaga cgatcctctc cgaggagggc 36600 ggccggttct accacgcgca gaaccggtac atcatcgtcg agtccgatat cgacgtggcg 36660 ccggaactgg cctcggagta ccgctggatg gcgctccacc agatggtcgg cctgctgcgg 36720 cacagccact acgtcaacgt ccaggcccgc agtctgatcg cgtgtctgca cagcctctcg 36780 ggggcgcagg ggcggaactg acccgcgccc tccccggatc tcctcccgct ctccccggcc 36840 ctgaaagggt gacgatgctc taccggcagc tcggacgtac ggcactgaag gtcagcccgc 36900 tctgtctggg caccctcaac ctcggcgtcc gtaccacccg tgacgaggcg ttcgccctca 36960 tggacgaggc cctggagcag ggcatcaact tcttcgacac cgccaaccag tacggctggc 37020 aggtccacaa gggcctgacg gaggagatca tcggagagtg gttcgcacag ggcggcggcc 37080 ggcgcgagcg cgtggtcctg ggcaccaagg tctgcaaccc gatgagcgat ctgcccaacg 37140 accaggggct gtcggcgcgg cacatcatcg cctcctgcga ggactcgcta cggcggctgc 37200 gcaccgactg gatcgatgtc taccagctcc acaacatcga cccgacggcg tcctgggacg 37260 aggtgtggca ggccatggag accctggtgc accagggcaa gatccgttac gtggggtcgt 37320 ccaacttcgc gggctggcat ctggccgacg cgcaggccgc ggcggcccgc cgtaacttcc 37380 tcggactcgt gtcggagcag tgctgctaca acctggcgac ccggtacgtg gagatggagg 37440 tcgtccccgc cgcgcgggcg cacggcatcg gagtgctggc ctggtcgccg ctgcacggcg 37500 gtctgctgag cggggcgctg cgcaagctgg acgaggggac ggcggtgaag acggcccagg 37560 gccgtgcgca gatcgcgctg cggaccatgc gggacaccgt cgagcagtac gagaagctgt 37620 gcgagagcat ctccgccgac ccgtcccagg ttgccctggc ctggctgctg tcccggccgg 37680 gtctcacggc cgccgtcatc ggcccgcgca ccaccgggca cctggcgagc gcgctggaga 37740 ccctggacat gacgctgccc gaggacatcc tggcgccgct ggacgaactc ttcccgccga 37800 tcggcaacgg tcagccggcg ccggccacct ggctcgcctg acgggcggga cgacttcccc 37860 ggccggtcac ccacgagcgt gtcaccggcc ggggggcacc agcggtcggg agccctgaca 37920 acgggcaccg ccactggtgc cggacccgaa caacgaccgc gtcccggccg ttcccacccc 37980 tgacacggag cagtccccac atgccgcctc atgtccgccc gatgcccgac atcacatccg 38040 aacggctccc ggaccaggac caccacctgc ccgccgagcg tgcccggccc gtgctgatca 38100 gcagcgtcgc ctccgactcg cacacctgga acctggtctt cctccaactg ctgatcgagg 38160 agctgggaca cgaggtcatc aacctcggtc cctgcgtgcc cgacgaactg ctcatcgccg 38220 agtgccgtga ccgccgcccc ggcctcgtcg tcatcagcac cgtcaacggc cacggctacc 38280 aggacgggct acgggtgatc gggaaactgc gcgcctgcga ggacctcgcg aacatccccg 38340 tcgtcatcgg cgggaagctc ggcgtctcgg gcccgggtca gtcgtacgcg gccgagttgg 38400 ccggcgccgg gttcgacgcg gtgttccccg acggggcgga ggccgtgtcc tccttcacca 38460 gatacgtcga gaagctcccg cagcgagtag tgtcttgacc ggattcggcg cctacgtccg 38520 ctccgtccac cggcgcggcg aactcgtcgt ccagccgcgg atgggattca gcggtacggt 38580 cgagatgcgc gccggtctcg ccgcgacccg ggcggcggac gcggccacgg tcggcaccat 38640 caccctggac agctacaccc gggtcgggga actcgccgca gccgaggagg cactccgctc 38700 cggcatcgcc ctcaacggct accccatcgt cacctacgac gaatccacca cccgtgaact 38760 cctcgccggg atcgcgggtg aggacttccc cgttcagatc cggcacgggt cggcgacccc 38820 cctgcacatc ttcggcgcgc tgacccgcgc gggcctggac gccaccgagg gcggccccgt 38880 ctcctactgc ctgccctacg gccggattcc gctggaacag tcggtgacca actggacccg 38940 ctgctgcgag gagttcgccc ggctgcgcgg gctgggccgt gaaccgcatc tggagacctt 39000 cggcggctgc atgctcgggc agctctgccc gcccagccag ctcgtcgcca tcagcatgct 39060 cgaagcgctc ttcttccacc agcacggcat tcgcagcatc tccctcagct acgcccagca 39120 gacccatcag ggacaggacg aggaagccgt gctggcgctg cgccggctcc accgcgaact 39180 gctgcccgat gccgactgcc acatcgtcat ctacgcctat atgggggtct atccgaccac 39240 ccccgagggg gcccacgcac tgctgggccg ggccgccgaa ctcgccgtcg ccaccggggc 39300 cgagcggctc atcgtcaaga ccgcggccga ggcccaccgc atccccacca tcggggagaa 39360 cgtggcggcc ctggagcacg cggccaccgt gtcccgcgcc gcccgccggg ccaccgcgct 39420 cccggccggt cactccgctg cgcccgctgc caccgacccc accgccgcgc tcacggcccg 39480 acccggtacg tacgcggacg gatccgccgc gctcacagcg ggccccggcg ccgcgcggga 39540 cggctccacc gactccgccg tctacgcgga ggcccgcgcc ctcatcgaag ccgtcatgaa 39600 ctgcggaccg gatgtcggca ccgcactgtt ccgcgctttc aagaggggat acctggacat 39660 cccctactgc ctccaccccg acaacatggg ccgcagccgg agttacatcg acgacaccgg 39720 gcggctgcaa tgggcggaga ccggaatgct gcccctgggg aatgccagaa aaagcggaac 39780 aggccgctcg gtatcgtcaa ccgatctgat atcggccctt tccttcgtgc agcggaccta 39840 tgaccaactg gcatttccgg aatcccggga gccgctccgg ataccccggc agcagcgccc 39900 ctaggggtgg ctagggggcg gataggggac ggctggagcg gcgctctccc ctagcatgag 39960 cgacgtaatc gaaccgtgag gtggtgtgaa tgtccaagcc cccgagtgcc aaggggactg 40020 tgccgttcgg tcaataccgg acgtggtatc gggtaacggg cgatctgcat tccggtaaac 40080 caccggtggt gctgttgcac ggtggtcccg gctccaccca cgactacctg ctggccatga 40140 cctccctcac cgaagccggc tggcccgtcg tccactacga ccagctcggc aacggcggat 40200 ccacccacct ccccgagaag ggcgaggact tctggaccgt ccagctcttc gaggacgaac 40260 tggacaacct cctcaaccag ctcggcatag ccggcgacta cgtgctcttc ggccagtcct 40320 ggggcgggat gctcggctcg gtgcacgccg cccgccgccc cgccggactg cgcggcctcg 40380 tcgtcgccaa cgcacccgcc tccatgaaga tctggctcca ggagatggcg cggctgcgcg 40440 cactgctccc gcccgacgtg caggagaccc tcctcaagca cgaggcggcg cggaccacgg 40500 acaccgagga gtacttccac gccatgcggg ccttctacga ccggcacgtc tgccggatcg 40560 tgccctggcc ccgggacttc gccgccacct tcatggagat ctacaacgac ccgacggtct 40620 acacgaccat gaacgggccg aacgagttcc atgtgatcgg caccctgcgc gactggtccg 40680 tcgaggactg cctgcccgac atccaggtgc ccaccatggt cctcatcggc cgtcatgacg 40740 aggccacccc cgcgaccgtc aagcccttcc tcgacctcgt gcccgacgtc cggtacgagg 40800 tgctggagaa ctccagccac gtaccgcacc tggaggagcc cgagcggttc cacgaggtga 40860 tgatcgacta cctcgaaagc ctggtgtgaa cgcgaccgtg gagacgacac agcacgacgt 40920 cgaggggacc ggcgcggccg gcgcgaccgc gatgctcttc cccgggatgg gacccgccgc 40980 gttctccgac gtcggccggt tcatggtgac caaccggtac accagggaac tcctcgcgga 41040 ggccgacgac accctcggct actccctcgt cgaccggttc cggcaggccg agggcgacta 41100 ctccgagtac gcccagatcg ccttcctggt caactgcgtc gccctcgccc gctgggccga 41160 gcagaccatg gacctcaccc cccggatctg cgccggagcc agcttcggcg agaagtccgt 41220 cgccgcctac agcggcgccc tcaccttcgc cgacgccgtc cggatgaccg ccggcctcgc 41280 ccgctgtatg gacgagtact tccgtacgga gcacctcggg gtcgtcaccc actccttcgt 41340 ccgcgcccct cgggagcggc tcgacgagat cctcgccgaa ctcgacgagc gcggcgaatg 41400 gcacgagatc tcctgccaca tcgaccacga cttcttcatg ctcaccctcc atgaacgcaa 41460 cagtgtctgg ctggagggcc ggctccggtc ggtgggcgcc atgccgctgt acgccatgcg 41520 gcccccgatg cacgccgccg ccttcggcgg gctgcgcgac aaggccgagg aggaggtcat 41580 cgcccccctc accttccacg acccgaccct gcccgtcgtc gccgaccagg acggcaaggt 41640 gctgaccacc ggcgacgagg tgcgcaccat gctcctggag agcttcgtcc gcccgctgcg 41700 ctggcccgac gtcatctcct cgctccagga ccagggcgtc acccgcgtct gtgtcgcggg 41760 ccccgacagc ctcttcgggc gggtcggcac caccacccgc gccttcgagg tcatcgcggc 41820 gaccccgcgg ctcgccctcc agccccgcgc gcgcaccacc tcgcgctgac cccgatcggg 41880 gttccgcccg cccaccacgg cggcgggacc ccgggggtcc ccgcaccacg gccgcccggc 41940 caccaccacc gtccgccccc ctgccggggg ccgaagggag cctcccatgt gggacgccca 42000 gttcgagaac ctcctccgcc gctacctccc gttcctctcc gccgaccagc cgctggagca 42060 ggacatcaac ctgcgtgaca tcggcctcga ctcgctcggc accgtcgagc tgctctccga 42120 gctggagaac acctacgacg tccacttcca ggacgaggcg ctcaccaagg agaccttcga 42180 gacccccggc gtgctctgga agaccctctc ccagatggtc gagccgcgcc actgaccacc 42240 cggcccggcg cacaacccgg gccgccagcc cggcccgacg gaggaccgat gcacgccgcc 42300 gaccacgccc tgcacgcccg cttcctgcgc gggctcgcct gcgcgcccga ccggcccgcc 42360 gtacggttcg gcgggcggac cctgacgtac gcgcaggccc accgcaccgc cctgacctgg 42420 gcgggttccc tgctgcgcgc cacgccggag cccccggccg ccgtcggtgt cctcgccgac 42480 aagggcatcc ccgcctatct gggcatcctg accgcgctct acgccggcgc cgccgtcgtg 42540 ccgctgcggc cggacttccc cgcggcccgt accgccgaga tgatgcgggc cgcgggggtc 42600 accgccgtca tagccgacgg tcgtggccgg cggctgctcc ccgaactgct cgccgaccgc 42660 cgggacaccg ccgtcctggc cgccgacgag gaaggcgccc ccgccgacga gagccccgcc 42720 gacgggagcg ccccgggccg ccgtgtcgcg atcgacgagg ggtacgcgct caccgcgccc 42780 cgggacgtcg tcccggacga caccgcgtac gtcctcttca cctccggctc caccgggcgg 42840 cccaagggcg tgccgctcag ccacggcaac atcgcccact acttcgaggt cctcgacgcc 42900 cgctacgact tcaccgcgga cgacgtcttc acccagacct tcgacctcaa cttcgactgc 42960 tcgctcttcg acctgttctg cgcctggggc gccggcgcga gcgtcatcca gatcccgccc 43020 caggcatacc gggacctgcc gtcccacctc gccgaacagg gcgtcaccgt ctggttctcc 43080 accccgagca gcatcgcgct ggtgcgccgg ctcggcggtc tggcacccgg ctcactgccc 43140 accctgcgct ggagcttctt cgcgggcgag gcactcaagt gcgccgacac ggaggactgg 43200 cagcgcgccg cgcccgcctc cttcgtggag aacctgtacg gccccaccga actcaccgtc 43260 accgtcaccg cccaccgctg gtccccggag gtctccccgg tcgtcggcgc caacggcgtc 43320 gtccccatcg gccccctcca caagggcctg gaccacgtcc tgatcgacgc cggtggactg 43380 ccccaccccg acaccgggga actctgcgtc accggacccc agatggcggg ccgctacctc 43440 gaccccgccg acgaccacgg ccgcttcctc gaccacgacg ggcgccgctg gtaccgcacc 43500 ggggaccggg tccgactggc ccccggcggg gaactcgtct acctcggccg gatggacgcc 43560 caggtccaga tccagggctg gcgggtggag ctcgccgagg tcgatcacgc cctccagggg 43620 tgcgagggcg tcggcgaggc cgtcaccgtc ggcgccgcca ccgacgcggg caccgagctg 43680 gtcgtcttct acacggcccc cgccccggtg ccgcccgtcc gcttcgccgc cgtgctgcgc 43740 gccaccctgc ccgacggtgt cgtaccacgg cactaccgcc atgtcgccga actgccgttg 43800 aattccaacc gcaagatcga ccggcgagca ctgaccgcac gtgccgagga actcctcggc 43860 tgagcacgtc cgagcggccg ggcaaccccc cggccgctca ctcattgccg caccccttac 43920 agcgacaggc ccctaggggc cgctaggggt atgtcggccg gcccgcaccg ggctagcctc 43980 actattgaca gacgtattcg ggggagttcg ccgtgtgtat tcaccagaca ggagagcggc 44040 gttgaacagc gtggccaaca tggtgtccga caatgccgat aaggatctcc gctacggcgg 44100 actcgtccac gatctcctgg cagactcagg aaaagcgaca ccgaattccg atgccatgga 44160 agacgcattc ggaacctgga cctatcaaga gctgctgaac catagtcagg cattcagcgc 44220 ctggctggac ggaaagggcg tcgcccgcgg cgaacgcatc gtcgtccagc tcccgaacat 44280 ccgccagacg gtcgccgtgt tctacggagc ctgccgccgc ggcgtcgtgt tcgtcccgct 44340 caacccgggc atgaagccct tccacctgcg gtccgtcatc gccgacgccg acccgcgcct 44400 ggtcatcgcc gaggacgaga ccgcggccga ccggctgcgt gacgtcaccg acctgccggt 44460 gtactccatc gactccctct gggcggatgt cgagcggctg cgcgacgcgg gcgccggagc 44520 cgaggccgtc gaggtctccc cggaggatct ggccgtcctc atctacacct ccggctccac 44580 cgcggccccc aaggcggtcg cctgccccca ccagcagatc gtgttcgccg cctcctcgat 44640 caacgccgta ctcggctacc acgccgaaga catcgtcttc tgccggatgt cggtctcctg 44700 ggacttcggt ctctacaagg tgctgatctc caccctcacc ggcgccaagc tcgtcctcgc 44760 gggcggtgag cccgacatcg cgctcgtcaa gtccctccgc gagagcggcg ccacgatgat 44820 gcccatcgtg ccgtccctgg cgagcatgct caccaccctc atccggcgcg accccgaggg 44880 cgccccgacg ctgcggatgt tcaccaacag cgccgccgcg ctgccccagg tcaccatcga 44940 cgccctgcgc tccgcgttcc ccggcgccca ggtcgtgcgc atgtacggcc agaccgagtg 45000 caagcgcatc tcgatcatgc cgccgcatct ggagcacgag cgacccgact ccgtcggtct 45060 gccgctgccc ggcaccacca tcgagatcct ggacgaggac ggcaccctcc tgccgcccgg 45120 tgagcccggc gagatcaccg tcaccggacc ccatgtcatg gccggctact ggcgcgcgcc 45180 cgagatcacc gcccgcgcct accgccgcga cgagaccacc ggcgcgatgc gcctgcacac 45240 cggcgactac ggccacctcg acgaggacgg attcctctac ttcggcggcc ggcgcgacga 45300 catgttcaag cgcaagggca cccggatgag caccgtcgag atcgaggccg cggccctcga 45360 catccccggc gtcaccgccg ccgtggcgct gcccccgacc gccacccggg acctggccct 45420 gtgtgtcgcg tccgacctcg aaccccatga cgtcctccgc agcctcgcgg agcggctcga 45480 accggcgaag gtccccgcga cctgccgtat cgtcaacgac ttcccgctca ccctgaacgg 45540 caagtccgag cgcaagcagc tcgcacgcct gctcgacggg agcgacaagt gaaccagtac 45600 gaagaactcg ccgaccagta cggcaccccg ctctacgtct acgacctcga ccgcgtcgcc 45660 gaggcccggc acgatctgcg cacctcactg cccgacgagg tcgagatcta ctacgccctc 45720 aaggccaacc cccacccgca ggtcgccggc gccctgcgca gcggcgaggg ccgcgagtgc 45780 cgcgccgaga tcagctccgt cggcgagctg gccgccgccc tcaccgccgg cttccgtgcc 45840 tccgagatcc tctacaccgg ccccggcaag accgacggcg aactggacga agcgatcggc 45900 aagggcgtca agaccttctg cgtcgaatcg ctgaccgacc tccagcacgt cggcgccgtc 45960 gccctgcgac acggcgtcgt cgccgactgc ctgctgcgca tcaacagcgc caccgccagc 46020 gccaccacca gcatccggat gaccggaacc ccctcacagt tcggcatcga cagcgagacc 46080 ctcgtcgacg ccatgcccga actgcgcgcc gtacccggca cccggatcac gggcctgcac 46140 ttcttccccc tcagcaacgc gagggacgag gccagcctca tcggcgagtt ccgccacacc 46200 atcgcctacg cggccggcct cgccgaggag accggtctca ccctggaatt cctcgacatc 46260 ggcggcggct tcgcccaccc ctacggcgcg cccggcgagc gccccgtcta ccgcgaactc 46320 cgcaccgagc tggccgccgc cctcgacgag cacttcccgc actggcgcga gggcgccccg 46380 cgcatcgcgg tggagaccgg ccgctaccag accagcggcg ccggaaccct gctcacccgg 46440 gtcgtcaaca tcaaggtcag ccggggccgg aagttcgtcg tcatcgacgc cgggatcaac 46500 accttcggcg gtatgtccgg cctcggccgg ctgctgccgg tcgccgtcga acccgagtac 46560 accggctccg ccgaagccac cgaactcacc gatgtcgcca gcctcgccgg ccccctctgc 46620 acccccggtg acatcctcgg ccgcgagatc cgcctgcccg aactggcccc cggcgacctc 46680 gtgaccatcc ccaacgcggg cgcgtacggc gtcaccgcga gcctgctgat gttcctcggc 46740 aggcccgcgc cggtcgaggt cgtcctgaag ggcggcaagg tcgtctccgc gtcccgactg 46800 gagcaccacc gcactccggc gacccccgga taaccacggc cgaccacccg ccgcgccccc 46860 ggtgacctcc gggggcggcc ggtaccgagc cccctgcgca ccacatccgg gaacgcccgc 46920 cacgggcgtt cccgcctttt cccgcgccgt cgccaccgag cccgcgcgcg ccgcaccacg 46980 tatgtcgccc gccttagcga ggagtaagcg aatgagcgag tccgagaacc ccgtttccgc 47040 caccacagcc ggtgcggatg aaaccccgga cacgcgtacg gcgctggctc ggcggctggc 47100 gggactgtcc cccgccgagc aggagcagca cctcgtcgac atggtgcacc ggcacacggt 47160 cgccgcgctc caggccgtcg ccccgctcac tccggaccag gtcgatgtgc agcgcccgtt 47220 cctggaactc ggcttcgact ccctcgccgc cgtggacctg cacaagcggc tcaccggcga 47280 gaccggcctc gaactgccgg tgaccgtcgc cttcgacttc cccacccccg tactcgtcgc 47340 cgaggagatc cgccggatcg ccttcggcat ccggcccgcc ccgctcgcgc ccgtcgtcgc 47400 caccggcaac ctggacgacg accccatcgc gatcatcggc atcggctgcc gtttccccgg 47460 cggcatcaac tccgccgagg aactgtggca gctcgtcatg gacgaggccg aggtgctctc 47520 cggattcccc accaaccgtg gctgggacgt cgagggcatc tacgaccccg acccgggcaa 47580 gcccggcaag agctacgtcc gcgaaggagg cttcctccag gacgcgggcg acttcgacgc 47640 ggacttcttc gggatctcgc cgcgcgaggc cctcgccatg gacccgcagc agcggctcgt 47700 cctggagacc gcctgggagg cgttcgaacg cgcgggcatc gaccccggct ccctccacgg 47760 cagcaaggcc ggtgtcttca tcggcgccga ggtccatgag tacggtacgc gcgtccatga 47820 agcccccgaa gggctcgacg gctacctcat gaccggcaac gcgcccagcg tcgcctccgg 47880 ccggatcgcc tacagcctcg ggctcgaagg ccccgccgtc accatcgaca ccgcctgctc 47940 gggctccctc gtcgccctgc acctcgccgc gcactcgctg cgccagggcg agtcctcgct 48000 cgccatcgcc ggcggtgtga ccgtcatggg caaccccggc atgttcgccg ccttcagccg 48060 gcagcgcggt ctcgccgccg acggccgctg caagcccttc gccgccgccg ccgacggcac 48120 cggcttctcc gagggcgtcg gcgtcttcgt cgttgagcgc ctcgccgacg cccgccgcaa 48180 cggccacccc gtgctgggca tcgtcaaggg ctccgccatc aaccaggacg gcgccagcaa 48240 cggactgacc gccccgaacg gcccctcgca gcagcgcctc atcctccagg ccctcgccaa 48300 cgccggtctg aagccggcgg acgtcgacac catggaggcc cacggcaccg gcaccaagct 48360 gggtgacccg atcgaggccc aggccatcct ggcgacctac gggcaggagc gcgaagaggg 48420 caggccgctc tggctcggct ccatcaagtc caacctcggc cacacccagg ccgcgggcgg 48480 cgccgccagc ctcatcaaga tgctgatggg gatgcgccac ggcaagctgc cgcgcagcct 48540 ccacatcgac gcgcccaccc cgcacgtcga ctggacgacc ggtgacgtcg cgctgctcac 48600 cgagacccgc gactgggacg cccccgaccg cccccggcgc gccggtgtct ccgccttcgg 48660 catcagcggc accaacgcgc acgtgatcat cgaggaggcg ccggagttcg agccgagcgc 48720 cgtggagccg gtggccgggt cgggggtgac accgccgtgg gtgctgtcgg cccggtcggc 48780 cgacgcgttg cgggggcagg ccgagcggct gctgtcgttc gtctccaccg acgccgatgt 48840 ctccgtggtg gatgtggcgt actcactcgg tgtgtcgcgt gcgggcctgg aacaccgcgg 48900 tgtggtgctg ggggagtcgc gcgaggaact gatcgcggct ctggagtcgc tggcgtccgg 48960 tgccgaggcg ccgggtgtgg tgacgggtcg ggtcgccgag ggccggttgg cgttcctgtt 49020 caccggccag ggtgcgcagc gcgtcggtat gggccgggaa ctcgccgccg aattccccgt 49080 gttcgccgct tccctggaag agacctgcga cctgctggac gtgggcctgg aggaccagga 49140 ccactcactg cgcgaggtgc tgttcgccga ggagggctcg gccgaggccg ccctgctgac 49200 gcggacggtg tacgcccagg ccgcgttgtt cgcggtggag gtggcgctgt tccggctggt 49260 ggagtcgttc ggtgtggtgc cggacttcgt cgccggtcac tcggtgggtg agatcgccgc 49320 cgcacacgtc gcgggcgtgt tctcgctgga agacgccacc atgctcgtcg ccgcccgggg 49380 ccggctgatg gacgccctgc cggagggcgg gacgatggtg gcggtgcagg ccaccgagga 49440 ggatgtgctc gccctgctgg agggggtgga ggacgcctcc atcgccgcga tcaacggccc 49500 cgacgccgtg gtcgtctccg gcaccgagac cggtgtcgcc cgggtggtcg acgtactccg 49560 ggaccggggc gcgaagacca agcggctcga cgtcagccac gccttccact caccgctcat 49620 ggagccgatg ctcaccgagt tccgccgggt ggccgaggtc ctcgaatacc aggcaccgcg 49680 gatcgccgtg gtgtcgaacg tgtccggatc ggtcgccggc accgaactgg ccacgcccga 49740 gtactgggtc acccacgtcc gcgaggccgt ccgcttcagc gccggcgtcc ggaccctgct 49800 cggcgccggc gtctcctcct tcctggagat cggtccggac ggtgtgctca gcgggatggc 49860 ccgtgggtcg gtctccgacg gcgccgacgt tggctgtgtc cccgtgatgc gccggggccg 49920 gggtgaggtg cgggagttcc tgaccggcct ctcccggatc gccgtacgcg gagtcccggt 49980 cacctgggag ccgctgatcg aaggcgcccg ccgcgtcgag ctgcccacct acgccttcca 50040 gcgccgctgg ttctggctgg aggccggccg ctcgaccacg gacgccctgg gcctgggcca 50100 gaccgccgcg gagcacccct tggtgggtgc cgtggtgggt ctggccggtg gtgatggtgt 50160 cgtcctgacc ggtcgggtgt cgttgcacac ccacccctgg ttggcggatc accaggtcgc 50220 cggggtgacg ctgctgccgg gtacgggctt cgtggagctg gcggtccgtg ccggtgacga 50280 ggtcggctgt ggccggttgg aggaactgac gctggaggca ccgctcgtcg tgcccgaccg 50340 gggcgccgtc cagctccagg tcgtcgtcgg cgcactggag gagtccgacg tccgcaccgt 50400 cagcgtctac tcccgcgccg aggaggacga cgtctggacc cgccacgcca ccggattcgt 50460 cggcgccgcc gtcgacggcg gactgaacct ggaggcatgg cccccgccgg gcgcccgggc 50520 ggtggacgtc agcgacgtct acgccggact ggccgaccag ggctacggat acggtcccgt 50580 cttccagggc ctccggtcgg tgtggcgcgg cgacggcgag gtgttcgccg aggtcgtgtt 50640 gccggaaggt gcacaggcgg acgcctccgc attcgggctg caccccgccc tgctggacgc 50700 cgcactgcac gccaccgact acctcgaccc ggagtccgcc gtcgagggca cgcatctgcc 50760 gttcgcctgg accggtgtct cgctgcacgc caccggtgcg tccgaactgc gggtacggat 50820 caccgccacc ggcaacgacg gatacgcgct cgacctcgcc gacaccaccg gccgccccgt 50880 cgccaccgtc cagtcgctcg tgctgcgccc ggtcaccgag gagcagctcc gcagcgccca 50940 gggcggcaac ggccccgaca gcctgttccg ggtggaatgg gcccccgtca ccgccgacct 51000 caccgcatcc ggcgccggct gggccgtgct cggcgccggt gctcccgaac tcgccgccgc 51060 cctcaccgcg gccggcaccc cgggcaccgc ctaccacggc acggccgagc tgagcgccgc 51120 cgtcgacggt ggcaccaccc ccgatgtcgt cgccgtccag ttgccgtcgg ccggcgccgc 51180 cgacgccgac ctcccggacg cagtccgcgc caccctgaac accgcgctgg agttcgtcca 51240 gaactggctg gccgacgagc gtctcgccga gaccaggctc gtggtcgtca cccgcgacgc 51300 cgtcaccgtc gacaccgccg cgggcggccc cgacctgacc gtcgcccccg tctggggact 51360 gatccgctcc gcgcaggccg agaaccccgg ccgcatcctg ctcgccgaca tcgacggcac 51420 cgaccagtcc cgtaccgccc tggccgcgat caccgccgcc gacgaacccg aactcgcctt 51480 ccgcaacggc aacgcgtacg ccccccggct ggtcaggtcc gtcagcgagg gcggcctcgt 51540 cccgccgtcg gacgccgcga gctggcgcct ggacgtgctg agccagggca ccctggagaa 51600 cctcgccctc atccccagcg acgccgacga gcggaccctc gccccgggcg aggtccggat 51660 cgccgtccgt gccgcgggag tcaacttccg tgacgtcctg gtggcgctcg ggatgtaccc 51720 gaccaaggcg gacatcggtg gtgaggccgc cggtctcgta ctcgaagtcg gccccggtgt 51780 caccgacttc acccccggcg accgggtgat gggtctcttc gacaccgcct tcggtccgca 51840 cgcgatcacc gaccaccgca ccctggtgcc gatgcccacc ggctggacct acgcgcaggc 51900 cgccacggcc ccgttggtct tcgccaccgc gtactacggc ctcgtggacc tcgccgaact 51960 gcgctccggc gaatcggcgc tcatccacgc cgcggccggc ggcgtcggca tggcggccgt 52020 ccagatcgcc cgccacctgg gcgccgaggt gtacggcacg gccagccccg gcaagtggaa 52080 cgcgctgcgc gccgccggac tcgacgacaa ccacatcgcg tcgtcccgtg acaccacgtt 52140 cgagcagaag ttcctcgcga actccggtgg ccgtggcgtc gatgtcgtcc tggacgccct 52200 caccggcgaa ttcatcgacg cgtcactccg gctgctgccg cgcggtggac gcttcgccga 52260 gatgggcaag accgatgtgc gcgacccgga gcgggtcgcg gccgagtacc ccggagtgcg 52320 ctaccgggcc ttcgacctct tcgaggcgga cctcgaccgg ctccgcgaga tcctgcgcga 52380 gctgctcgcc ctcttcgaga gcggtgcgct gcggccgctg ccggtgcgtg catgggacat 52440 ccgcaagtcc aaggacgcct tccgccatat cgcccaggcc cggcacatcg gcaaggtcgc 52500 cctcaccatg cccacgggtg gtttgggtga tggtgtggtg ttggtgacgg gtggtacggg 52560 tgggttgggt gcgttggtgg cgcggcatgt ggtggtggtg catggggtgc gtcgtttggt 52620 gttggtgtcg cgtcgtgggt tgggtgctcc gggtgcggtg gggttggtgg ctgagttgga 52680 gggtttgggt gctgtggtgg aggtggtggc gtgtgatgtg agtgatcgtg tggcgttggc 52740 gggtgtggtg gggggtattg ggtcggatct gtcggctgtg gtgcatacgg cgggtgtggt 52800 ggatgacggt gtggtgggtt cgttgtcggt ggggcggttg tcgtcggtgt tgggtccgaa 52860 ggcggatgcg gcgtggtatt tgcatgagtt gacggtgggg ttggatctgt cggcgtttgt 52920 gttgttctcg tcggttgctg gtgtggtgga tggtgcgggt caggggaatt atgcggcggc 52980 gaatgtgttt ttggatgggt tggctgtggt gcggcgtggt ttggggttgc cgggtacgtc 53040 ggtggcgtgg gggttgtggg agggggctgg tatgggtgcg gtgttgggtg aggctgatgt 53100 gttgcggatg agtcgttcgg gtgtgttggg gttgtcggtg ggtgaggggt tggggttgtt 53160 tgatgtggcg ttgggtgagg atgtggcggc gttggtgccg gtgcggttgg atttgggggc 53220 tttgcgttcg cgggttgatg gggtgcctgc ggtgttccgg tcgttggtgc gggtgccggt 53280 gcgtcgttcg gtgggtgtgg gtgtttcggg tggtggtgag gtgtcgttgg agcggcgttt 53340 ggtggtgttg gatgcgggtg agcgtgagcg ggtgttgttg gagttggtgc ggtcgcatgt 53400 ggcggctgtg ttgggttatg agggtgcggg gtcgattgag ccgggtcgtg cgttcagtga 53460 tatcgggttc gattcgttgt cggcggttga gctgcggaat cgtttgaatg gtgagacggg 53520 gctgcggctg ccggcgacgc tgatcttcga ttaccccacc cctcaagccc tcgccgaata 53580 cgtcatcgtc gccctgctcg gcgaggaggc ggccaacgcc cccgccctgc cgcccaccga 53640 ggcccccacc gtcaccggaa ccgatgacga ccccgtggtc atcgtcggca tgggctgccg 53700 cttccccggc gacgtccgta cccccgagga cctgtggcga ctggtctcca acggcagcga 53760 cgccgtgacc cccttccccg acaaccgcgc ctgggacatc gaaggcatct acgacccgct 53820 gcccggcgtg tccgggaaga cgtacgcccg cgagggcggc ttcctgcacg acgcggccga 53880 gttcgacccc gagttcttcg ggatctcgcc gcgtgaggcc ctcgccatgg acccccagca 53940 gcgactgctc cttgagacgt cctgggaggc catcgagcgg gcgggcatcg acccgaacag 54000 cctgcgcgga acccagaccg gcgtcttcgc cggagtcatg cagaccgact acggcaacgg 54060 cggcgcccgg ctcgccgagg acgtcgaggg ctacatcgcc aacggcacgc tcggcagcat 54120 cgtctccggc cgggtctcct acgccctggg tctggagggc ccggcggtca cgatcgacac 54180 cgcctgctcc tcctccctcg ttgccatgca ctgggcggcc cacgccctgc ggcagggcga 54240 gtgctcgctc gccctggccg gcggcgtgac cgtcatgtcg acgccggaga ccttcgtcga 54300 cttcagcctt cagcgcggcc tcgctcccaa cggtcggtgc aaggcgttct cggcggacgc 54360 cgacggcacc ggctggggcg agggcgtcgg cgtcctggtc cttgagcggt tgtcggacgc 54420 ccgccggaac gggcatcagg tactcgcggt catccgtggt tccgcgctga accaggacgg 54480 tgcgagcaac ggcctgacgg ctccgaatgg tccctcgcag cagcgggtga tccgccaggc 54540 cctcgtgagc gccggtctga ccacgtcgga cgtcgacgcg gtcgaggcgc acggcaccgg 54600 caccacgctc ggtgacccga tcgaggccca ggcgctgctg gccacctacg gccaggagcg 54660 ggacgcggac cagccgctct ggctcggctc cgtcaagacg aacgtgggtc acacgcaggc 54720 cgcggccggt gttgccggtg tgatcaagat ggtgctcgcg atgcgggccg gtgtgctgcc 54780 gaagacgctg catgtcaccg agccgtcgcc gcacgtggac tggtccgccg gcgccgtgga 54840 gctgctgacg gagacgcgcg actggccgga gaccggccgt ccgcgccgcg ccggtgtgtc 54900 gtcgttcggt gtgagcggca cgaacgcgca cgtcatcgtc gagcaggcac ccgccgtcga 54960 agaggagccg acgcgcgccc ttccggcact cccggtcccg tggtccatct cggccaagtc 55020 ggccgacgca ctgcgcggcc aggcccaggc cctgtcgtcg ttcgtctctg ccgccggtga 55080 tgtgtcggtg gtggatgtgg cgtactcgct gggtgtgtcg cgtgcgggtc ttgagcatcg 55140 tggtgtggtg gtgggggagt cgcgtgcgga gttgctcgtg gctctggagt cgttggcgtc 55200 cggggttgag tcgccgggtg tggtgacggg gcgggtcgcc gagggtcggt tggcgttcct 55260 gttcacgggg cagggtgcgc agcgggtcgg catgggtcgg gaactcgctg ccgaattccc 55320 ggtgttcgcg gcgtctcttg agcagacgtg tgacttgttg gagcgtgccg gggttgcggt 55380 gcgtgaggtg ctgttcgctg aggagggttc ggccgaggcc gccctgctga cgcggacggt 55440 gtatgcgcag gctgcgttgt tcgccgtcga ggtggcgctg ttccggttgg tggagtcgtt 55500 cggtgtggtg ccggactttg tcgccgggca ttcggtgggt gagatcgccg ccgcgcatgt 55560 cgcgggcgtg ttctcgcttg aggatgcggt gtccctggtc gcggctcgtg gtcggttgat 55620 ggatgcgctg ccggagggtg gggcgatggt ggcggtgcag gccaccgagg aggatgtgct 55680 tgccctgttg gagggggtgg aggacgcctc catcgccgcg atcaacggcc ccgacgccgt 55740 ggtggtctcc ggcaccgaga ccggtgtcgc ccgcgtagtg gacgtactcc gggagcgggg 55800 tgcgaagacc aagcggctcg tggtgagtca tgccttccac tcgccgctga tggagccgat 55860 gctcgccgac ttcgccaccg tcgtggaggg gctctcgtac aaggctcccg ccatcccggt 55920 cgtgtcggga tcagttgtcg ggagcgagtt gtcgacgccg ggttactggg tgcggcatgt 55980 tcgtgaggcg gttcgtttcg gtgcaggggt ggagaccctg ctcggcgctg gtgtgtcgtc 56040 gttcctggag atcggtccgg acggtgtgct gagcgggatg gcccgtacgt ccgtgcctga 56100 gggtgcggat gtggagtgcg cgccgctgat gcgccgggac cgcgccgagg tgcgggagtt 56160 cctgaccggt ctctcccgtc tcgccgtacg cggtgtcccg gtcgcctggg agtcgctggt 56220 cgaaggcggc cggcgggtcg agctgccgac gtacgccttc cagcgtcgcc ggttctggct 56280 ggaggccggc cgttcggtga cggatgcttc gggtctgggc cagaccgccg cggagcaccc 56340 cttggtgggt gccgtggtgg gtctggccgg tggcgatggt gtggtgctga ccggtcgggt 56400 gtcgttgcac acccacccct ggttggcgga tcaccaggtc gcgggggtga cgctgctgcc 56460 gggtacgggc tttgtggagc tggcggtccg tgccggtgac gaggtcggct gtggccggct 56520 ggaggaactg acgctggagg ccccgctggt cgtgcccgac cggggcgcgg tgcagctcca 56580 ggtcgtcgtc ggcgcactgg agacgtccgg tgtccgtacc gtcagcgtct actcccgcgt 56640 ggaggaagag agcgcggatg acacctgggt ccgccacgcg accggcgcgc tcatggccgc 56700 cgccgaggag cccggattcg acctcaccgc atggccgccg gctggtgcgc gggcggtcga 56760 tgtgagtgac gcttacgccg gactggcgag ccagggctac gggtacggac ccgtcttcca 56820 ggggctgacg gccgcctggc gcaagggccg ggaggtcttc gcggagatca cgctgccgga 56880 ggccgcgcag gtggacgctt cggcgttcgg gctgcacccc gcgctgctgg acgctgcgct 56940 gcacgccacc gactacctcg atcaggagag cgccgagggc acgcatctgc cgttcgcgtg 57000 gagcggtgtc tcgctgcacg ccgccggcgc gtccgcgctg cgggtacgga tcgtcgcgac 57060 cggcaaggac ggatacgcgc tcgacctcgc cgacagcaca ggccgccccg tggccactgt 57120 tcagtcgctg gtcacccgtc ccgtcaccgc ggaccaactg tccgaagcct cggccactca 57180 gcaccagtcg ctcttccgga tggagtggac cgccacgacc gccccggccg cgaccgctga 57240 tgtccgctgg gcgcttctcg gcgagccggt cgcggaactg ggcgacctcg cgggcttcgg 57300 ccgtacgacc gcgtacgcct cgctcgccga cctggccgcc gccgacgcgg acaccgttcc 57360 ggacctcgtc gtcctgccgc tgggcagccg gatggctgag ggaagtgacg taccggaagc 57420 ggtacgggag aacctcggtc aggtcctggc gacgatccag cagtggaacg acgactcccg 57480 gttcgacggc tcccggctcg tggtgctgac acacggtgcc gtctcggtct ccgacgatga 57540 atcgctcacc gcactggatc tggctccggt ctggggtctg gtccgctcgg ccatggccga 57600 gactcccggc cgcttcctgc tggtggacac cgatgggacc gacccgtcga ccgacgcgct 57660 gcgtcatctg gccgaactcc aggaggccga gttcgcgctg cgcgagggcg agatacgcgt 57720 acctcggctc gcgcgcgttc cggtggccgg agctggtgcc gacatcacgg gtggtttggg 57780 tgatggtgtg gtgttggtga cgggtggtac gggtgggttg ggtgctgtgg tggcgcgtca 57840 tgcggtggtg gtgcatgggg tgcgtcgttt ggtgttggtg tcgcgtcgtg ggttgggtgc 57900 tccgggtgcg gtggggttgg tggctgagct tgagagcttg ggtgctgtgg tggaggtggt 57960 ggcgtgtgat gtgagtgatc gtgtggcgtt ggctggtgtg gtggggggta ttgggtcgga 58020 tctgtcggct gtggtgcata cggcgggtgt ggtggatgac ggtgtggtgg gttcgttgtc 58080 ggtggggcgg ttgtcgtcgg tgttgggtcc gaaggcggat gcggcgtggt atttgcatga 58140 gttgacggtg aggttggatc tgtcggcgtt tgtgttgttc tcgtcggttg ctggtgtggt 58200 ggatggtgcg ggtcagggga attatgcggc ggcgaatgtg tttttggatg ggttggctgt 58260 ggtgcggcgt ggtttggggt tgccgggtac gtcggtggcg tgggggttgt gggagggggc 58320 tggtatgggt gcggtgttgg gtgaggctga tgtgttgcgg atgagtcgtt cgggtgtttt 58380 ggggttgtcg gtgggtgagg ggttggggtt gtttgatgtg gcgttgggtg aggatgtggc 58440 ggcgttggtg ccggtgcggt tggatttggg ggctttgcgt tcgcgggttg atggggtgcc 58500 tgcggtgttc cggtcgttgg tgcgggtgcc ggtgcgtcgt tcggtgggtg tgggtgtttc 58560 gggtggtggt gaggtgtcgt tggagcggcg tttggcggtg ttggatgcgg gtgagcgtga 58620 gcgggtgttg ttggagttgg tgcggtcgca tgtggcggct gtgttgggtt atgagggtgc 58680 ggggtcgatt gagccgggtc gtgcgttcag tgatatcggg ttcgattcgt tgtcggcggt 58740 tgagctgcgg aatcgtttga atggtgagac ggggctgcgg ctgccggcga cgctgatctt 58800 cgattacccc accccccaag ccctcgccga tctcatccag gagaagacgc tgggtctggt 58860 cgacgccgcc gcggccaccg tgtccaccac ggtgtcccgc accgatgacg agcccatcgc 58920 catcgtcggc atgggctgcc gctacccggg agacgtccgt acccccgagg agctgtggcg 58980 gctcgtcgcc agcggcacgg acgccgtcag cctcttcccc gaggaccggg gctggaacgt 59040 cgactccatc tacgacccga cgcccggcct gtccgggaag acgtacaccc gtgagggcgg 59100 cttcctgcac gacgcggccg agttcgacgc cggcttcttc gggatctcgc cgcgcgaggc 59160 cctcgccatg gacccgcagc agcgactgct ccttgagacg tcctgggagg cgatggagcg 59220 ggccggcatc gacccgaaca gcctgcgcgg cacccagacc ggcgtcttcg ccgggatcat 59280 gtaccacgac tacgggtccc gggtgaccca gccgtcggag gaggtcgagg gctacctcgg 59340 caacggcagc gcgggcagca tcgcgtccgg ccgggtctcc tacaccttcg ggttcgaggg 59400 tccggcggtc acggtcgaca ccgcctgttc ctcctcgctc gtcgccctcc actgggcggc 59460 tcaggccctg cgccagggcg agtgcagcat ggcgctcgcg ggcggtgtga ccgtcatgtc 59520 gacgccggag accttcgtcg acttcagcct ccagcgcggc cttgccacga acggccggtg 59580 caaggcgttc tcgtccgacg cggacggaac tggctggggc gagggcgcgg gaatgctcct 59640 gctggagcgg ttgtcggacg cgcggaagaa cgggcacgaa gtactcgcgg tcatccgtgg 59700 ttcggcgctg aaccaggacg gtgcgagcaa tggtctgacg gcgccgaacg gtccttcgca 59760 gcagcgggtg atccgccagg cgctggccaa cgccggtctg tcggccgccg aggtggacgc 59820 ggtcgaggcg cacggtacgg gtacgaagct gggtgacccg atcgaggcgc aggcgctcct 59880 ggcgacctac ggccaggagc gggacggcga ccagccgctg ctgctgggct cgatcaagtc 59940 gaacgtcggc cacacgcagg cggccgccgg tgtcggcggt gtgatcaaga tggtgatggc 60000 catcaggaac ggtgtgctgc cgaagacgct gcatgtcacc gagccgtcgc cgcacgtgga 60060 ttggtccgct ggtgcggtgg agctgttggc ggaggctcgg gagtggcctg agacgggtcg 60120 tccgcgtcgt gcgggtgtgt cgtcgttcgg tatcagtggg acgaatgcgc acgtgatcgt 60180 ggagcaggcc cccaccgacc agccggcgcc gctgagcgag ccggttggtg atgtgccggg 60240 tcttccggtg ccgtggatcg tctcggccaa gtccgcggag gcgttgcggg cgcaggcggg 60300 tcggttgggt tcgttcttgg gtgagaccgg tgttgttgat gtgccggcgg tgggttggtc 60360 gttggtgcgg ggtcgttcgg tgttcgcgca tcgggcggtt gtggtgggtg gtgagtggga 60420 tgagctgttg gccggtgtgg ctcgggtcgc tgagggtgtg gatgactcgg ttgtgtcggg 60480 tgtggcggat gtgtcggggc gtcgggtgtt tgtgttcccg gggcagggtt cgcagtgggt 60540 tggtatggcg caggggttgt tggattcgtc ggtggtgttc acggagcgga tgacggagtg 60600 tgctgcggcg ttggatccgt tggtggagtg gtcgttgttg gatgtggtgc ggggtgtgga 60660 gggtgcggcg tcgttggagc gggtggatgt ggtgcagccg gtgttgtggg cggtgatggt 60720 gtcgttggcg tcggtgtggc gttcggtggg tgtggtgccg gatgcggtgg tgggtcattc 60780 gcagggtgag atcgcggctg ctgtggtggg tggttggttg tcgttggtgg atggtgcgcg 60840 ggtggtggcg ttgcggtcgt tggcgattcg tgaggtgttg gcgggtggtg gtggcatggt 60900 cgcggtccag gctgccgagg atgaggttgc tgggtggctt gagggtgtgg agggggtggg 60960 gattgctgcg gtgaatggtc cgcgttcggt ggtgatctcg ggtacgcgtg cgggtttgga 61020 tgcgtgtgtg gagttgtggt ctgggcgggg gacgtgggtg aagcgggttc cggtggacta 61080 tgcctcgcat tcggctgagg tggagcgggt gcgtgagcgg gtgctggcgg atctggcgag 61140 tgtgacgggt ttgtcggggt cggtgccgat gttgtcgacg atgacgggtg actggattgt 61200 tgagggtcag gtcggggccg ggtattgggt ggagaatctg cgtcgtccgg tgttgttcgc 61260 ggacgcgacg aggcggttgg cgtcggaggg cttcggtgcg ttcgtcgagg tgagcgcgca 61320 tccggtcctg gtgatgggca tcgaggagac gatcgaggcg ctgaggtcgg gcgccgccga 61380 tggtgcgaag tccggtgctg gtgaggagag ttcctccgct gtggtggcgg tggggacgtt 61440 gcgtcgtggt gagggtggtt gggatcagtt cctgcgttcc ctcgcggggc tcttcgtccg 61500 gggtgcggtg gcaccggatt gggagtcgtt gttgggtggt gtgcgtcctc gggttgattt 61560 gccgacgtat gcgttccagc gtgagcggtt gtggctggat gcgggtgtgg tggcggggga 61620 tgtgtcgggg ttgggtcagg tggtggtggg tcatccgttg ttgggtgctg gtgtgggtgt 61680 tgctggtgag ggtgggggtg tgttgtttac gggtcgtttg gggttgggtt cgcatccgtg 61740 gctgggtgat catgcggtgt cgggtgtggt gttgttgccg ggggctgcgt ttgtggagtt 61800 ggtggtgcgt gcgggtgatg aggtggggtg tggtcggttg gaggagttga cgttggcggc 61860 tccgttggtg gtgccggagc gtggttcggt gcggattcag gtggtggtgg gtgctggtga 61920 tgggtcgggt gcgcgttcgg tgggtgtgtg gtcgtcggtg ggggatgagg gtgtgggtgg 61980 ggagtgggtg tgtcatgcgt cgggtttgtt gacggctgat gtgggtgtgg cgccggtgtt 62040 gggtggtgtg tggccgccgg tgggtggtgt ggcggtggat gtgtcgggtg tgtatgaggg 62100 gttggcgttg gaggggtatg agtatgggtc ggtgtttcgg gggttgaggt cggtgtggcg 62160 tcgtggggat gaggtttttg ctgaggtggc gttgggtgag ggtgtggggg tggaggggtt 62220 tggtttgcat ccggcgttgt tggatgcggc gttgcaggct gctgggtttg gttcgtttgt 62280 gccggagtcc gaggcagggt ctgaggcggg ttcgggtggg gtgcggttgc cgttctcgtg 62340 gtcgggtgtg tcgttgtttg cgtcgggtgc ttcggtgggg cgggtgcggt tgtggccggt 62400 gggtggggat ggttttggtg tggagttgtt tgatggggtg gggatgccgg tggcgcgggt 62460 ggatgcgttg gtgacgcggg agattagtgc gggtcagttg ggtgcggctg ctggtgccgg 62520 gtcgttggtg ggtggggagt cgttgttccg ggtggagtgg gctcctgtgt cgggtgtcgc 62580 gccggcttct gctggtgtgg gtggttgtgt ggtggtgggt gcggggagtg tgttgtctgg 62640 ttttggggag gtggttccgg atctggcggc ggtttccgcg ggttctgcgg atggggtggg 62700 tgtgccgggg tgggtgttgg tggatgtgga tgcgtggttg ggtgcggatc tggctgtggg 62760 tgtggtgtcg ggtgagggtg ttccggtggt ggcgcgtggt gtggtggcgc gggtgttggg 62820 gttggtgcgg gagtggttgg gggatgagcg gtgggtgtcg tcgcggttgg tgtgggtgac 62880 gcgtggtgcg gtgggtgctc gggtgttgga tgaggtgtcg ggtgtggtgt cgtcggggtt 62940 gtgggggttg gtgcgggctg ctcagtcgga gcatccggac cggttcgcgc ttcttgatct 63000 ggacagtgcc accgccgtgg atgccgttcg tgatggtgtg ttggggttgc tggcggctgg 63060 tgagccgcag ttggtggtgc gtgagggtga ggtgctggcc gcacggctga cccccgccca 63120 caccaccgat gaacccaccg gccaggagtt cggcaaggcg gcgaccggta cggtcctcgt 63180 caccggtggc accggcggcc tcggtgccgt cgtcgcacgg cacctggtca ccgagcacgg 63240 cgcacagcgt ctgctcctca ccagccgtcg cggtatcaac gcgccgggag ccgccgaact 63300 cgtcgcggaa ctcgccgagc tgggtgccag ggccgacgtc gcagcctgcg acgtctcaga 63360 ccgggcggca ctcaaggaac tgctcgccgg cgtaccgggg gacgcaccgc tcaccgcggt 63420 cgtccacgcg gccggcgtgc tggacgatgg tgtgatcgag tcgatgacgg ccgatcgcct 63480 ggacgccgtc atgcggccga aggtcgacgc ggcctggcat ctgcacgagc tgaccgccga 63540 ccgggaattg gatgcgttcg tcctcttctc ctccgcggcc ggcacgctgg acggtgccgg 63600 acagtccaac tacgcggcgg cgaatgtgtt cctggacgcg ctcgcgcagt accgccgtgg 63660 tcagggtctg gcgggtctgt cgctggcctg gggcctgtgg ggcgagagca ccggcatggt 63720 gggcgcgctg gagggttcgg acctcgaccg catcggccgc tccggcgtcc gggcgctgtc 63780 gtcggccgag gggctcgcgc tcttcgacgc cgccgccgtg ctgggcgagc cggccgtact 63840 gccggtcgcg ttggacctcg gcgtactccg gacacagccc cggaaccagg ttccggcgat 63900 cctgcgcggg ttcgcggcgg gcccgacccg gcgcaccgcg gtcactggtg ggcccgagac 63960 ggaccaggag gcgctcacgc ggcgcctcgc ttccctctcg cccgccgacc gggaccgctt 64020 cctgttggat ctggtccgta cgcaggtggc cggggtgctc gggtactccg gtccggacgc 64080 gatcgatccg cagcgcgggt tccaggagct gggcgtcgac tcgctggccg ccgtacagat 64140 ccgtaaccgg ctcggcgcgg ccacgggtgt ccggccgccg acgacgctcg tcttcgacta 64200 tccgaccccc gacgcggtgg ccgggtactt caaggagcac ctcgtcatcg aggaggagga 64260 ctcgaccgcg gagctgatgc gggagatcgc ccggctggag gccgcggtca cctccgcggc 64320 ctcatcggcg ggcggcgcgg gcctggcacc cgccgtggac cggctgcggg cgatggcggc 64380 gaagctggcc gacgcggatg cccagcgggc cgacgaggac gacccgggcc tggagtccgc 64440 gaccgcggac gaactgttcg acatcctcga cggtgagctg tccacggact ga 64492 2 355 PRT Streptomyces halstedii sp.HC-34 2 Val Lys Ala Leu Val Leu Ser Gly Gly Ser Gly Thr Arg Leu Arg Pro 1 5 10 15 Ile Thr His Thr Ser Ala Lys Gln Leu Val Pro Val Ala Asn Lys Pro 20 25 30 Ile Leu Phe Tyr Val Leu Glu Ser Ile Ala Glu Ala Gly Ile Thr Asp 35 40 45 Val Gly Ile Val Val Gly His Thr Ala Pro Glu Val Gln Asp Ala Val 50 55 60 Gly Asp Gly Ser Ala Phe Gly Val Asp Val Thr Tyr Ile Ala Gln Asp 65 70 75 80 Glu Pro Leu Gly Leu Ala His Ala Val Arg Ile Ser Arg Asp Tyr Leu 85 90 95 Gly Asp Asp Asp Phe Val Met Phe Leu Gly Asp Asn Phe Ile Ile Asp 100 105 110 Gly Val Thr Gly Leu Val Asp Arg Phe Arg Asp Glu Arg Pro Asp Ala 115 120 125 Gln Ile Leu Leu Thr Arg Val Pro Asp Pro Arg Ala Phe Gly Val Ala 130 135 140 Val Leu Asp Glu Gln Gly Arg Val Ile Gly Leu Glu Glu Lys Pro Glu 145 150 155 160 His Pro Arg Ser Asp Leu Ala Leu Ala Gly Val Tyr Phe Phe Thr Pro 165 170 175 Leu Ile His Glu Ala Val Trp Ala Val Lys Pro Ser Trp Arg Gly Glu 180 185 190 Leu Glu Ile Thr Asp Ser Ile Gln His Leu Ile Asp Thr Gly Ala Asp 195 200 205 Val Arg Ser His Ile Ile Asp Gly Tyr Trp Lys Asp Thr Gly Asn Val 210 215 220 Val Asp Ile Leu Glu Val Asn Arg Ile Ile Leu Glu Ser Val Glu Thr 225 230 235 240 Ala Ile Asp Gly Asp Val Asp Ala Asp Ser Glu Ile Ile Gly Arg Val 245 250 255 Val Ile Glu Lys Gly Ala Thr Val Lys Gly Ser Arg Ile Val Gly Pro 260 265 270 Ala Leu Ile Ala Thr Gly Thr Glu Ile Arg Asp Ser Tyr Val Gly Pro 275 280 285 Phe Thr Ser Val Ala Glu Asn Cys Arg Ile His Asp Ser Glu Leu Glu 290 295 300 Phe Ser Ile Met Met Arg Asp Ser Ser Leu Thr Gly Ile Arg Arg Ile 305 310 315 320 Glu Ala Ser Leu Ile Gly Arg His Val His Gly Thr Ala Val Pro Arg 325 330 335 Val Pro Asn Ala His Arg Leu Val Leu Gly Asp His Ser Thr Phe Gln 340 345 350 Ile Ser Ser 355 3 323 PRT Streptomyces halstedii sp.HC-34 3 Met Ser Thr Arg Leu Leu Val Thr Gly Ala Ala Gly Phe Ile Gly Ser 1 5 10 15 Ala Tyr Val Arg Gly Leu Leu Thr Asp Gln Pro Asp Leu Arg Val Thr 20 25 30 Val Leu Asp Ser Leu Thr Tyr Ala Gly Asn Arg Ala Asn Leu Asp Leu 35 40 45 Thr His Pro Ser Leu Asp Leu Val Glu Gly Asp Ile Cys Asp Thr Glu 50 55 60 Leu Val Asp Arg Leu Thr Ala Glu Ala Asp Gln Ile Val His Phe Ala 65 70 75 80 Ala Glu Ser His Val Asp Arg Ser Ile Thr Gly Ser Ala Glu Phe Ile 85 90 95 Arg Thr Asn Val Leu Gly Thr His Thr Leu Leu Asp Ala Ala Leu Arg 100 105 110 His Gly Ile Asp Arg Phe Val His Ile Ser Thr Asp Glu Val Tyr Gly 115 120 125 Ser Ile Glu Lys Gly Ser Trp Pro Glu Thr Asp Pro Leu Arg Pro Asn 130 135 140 Ser Pro Tyr Ser Ala Ser Lys Ala Ser Ser Asp Leu Leu Ala Leu Ala 145 150 155 160 Tyr His Arg Thr His Gly Leu Asp Val Arg Val Thr Arg Cys Ser Asn 165 170 175 Asn Tyr Gly Pro Tyr Gln His Pro Glu Lys Val Ile Pro Leu Phe Val 180 185 190 Thr Asn Leu Leu Asp Gly Lys Arg Val Pro Leu Tyr Gly Asp Gly Gln 195 200 205 Asn Val Arg Asp Trp Leu His Val Glu Asp His Cys Ala Ala Ile Glu 210 215 220 Cys Val Arg Thr Arg Gly Gly Ala Gly Glu Ile Tyr Asn Ile Gly Gly 225 230 235 240 Gly Thr Glu Leu Ser Asn Arg Glu Leu Thr Gly Leu Leu Leu Glu Ala 245 250 255 Cys Gly Ala Asp Trp Asp Ser Val Glu Tyr Val Thr Asp Arg Lys Gly 260 265 270 His Asp Leu Arg Tyr Ser Val Asp Trp Ser Lys Val Ala Asp Leu Gly 275 280 285 Tyr Thr Pro Ala His Asp Phe Arg Ala Gly Leu Ala Glu Thr Val Asp 290 295 300 Trp Tyr Arg Ser Asn Arg Thr Trp Trp Glu Pro Ala Lys Tyr Gly His 305 310 315 320 Ser Pro Ala 4 419 PRT Streptomyces halstedii sp.HC-34 4 Met Arg Val Leu Met Thr Val Phe Ala Asn Arg Ser His Leu Tyr Asn 1 5 10 15 Met Val Pro Leu Ala Trp Ala Leu Thr Thr Ala Gly His Glu Val His 20 25 30 Ile Ala Ser His Pro Asp Asn Val Gln Ala Ile Ser Asp Ser Gly Leu 35 40 45 Thr Ala Val Pro Val Gly Asn Asp Leu Asn Ile Met Ala Leu Ala Gln 50 55 60 Ser Thr Pro Arg Glu Glu Met Val Asn Gly Gly Ala Leu Thr Leu Asn 65 70 75 80 Glu Thr Arg Pro Glu Lys Leu Thr Trp Gln Tyr Ile His Asp Val Phe 85 90 95 Ala Gln Tyr Ser Gln Ile Tyr Glu Tyr Met Ala Asp Ser Thr Met Thr 100 105 110 Ala Asp Leu Val Ala His Ala Arg Gln Trp Gln Pro Asp Leu Val Ile 115 120 125 Trp Asp Ala Leu Thr Tyr Ala Gly Pro Ile Ala Ala Glu Ala Val Gly 130 135 140 Ala Pro His Val Arg Met Leu Phe Gly Leu Asp Gln Trp Gly Arg Met 145 150 155 160 Arg Asp His Phe Asn Arg Leu Thr Gly Glu Arg Ala Ala Asp Asp Arg 165 170 175 His Asp Pro Leu Ala Asp Trp Leu Ala Thr Lys Gly Glu Pro His Gly 180 185 190 Val Ala Phe Thr Glu Ser Leu Val Thr Gly Thr Thr Thr Leu Ala Val 195 200 205 Ala Pro Pro Trp Met Ser Phe Pro Ser Glu Gln Pro Ala Leu Ser Met 210 215 220 Arg His Leu Pro Phe Asn Gly Pro Ala Val Leu Pro Asp Trp Leu Arg 225 230 235 240 Glu Ala Pro Ser Arg Pro Arg Val Cys Leu Thr Leu Gly Leu Thr Leu 245 250 255 Arg Glu Leu Ala Asp Asp Asn Val Thr Leu Ala Asp Phe Val Asn Ala 260 265 270 Val Ala Asp Ile Asp Ala Asp Val Val Ala Thr Phe Ser Ala Glu Gln 275 280 285 Val Ala Glu Ile Gly Asp Leu Pro Asp Asn Val Arg Ala Val Asp Phe 290 295 300 Val Pro Leu His Ala Leu Leu Pro Ser Cys Ala Ala Ile Val His His 305 310 315 320 Gly Gly Gly Gly Thr Arg Thr Asn Ala Ile Arg Tyr Gly Val Pro Gln 325 330 335 Leu Ile Val Pro Asn Trp Leu Trp Asp Glu Gly Tyr Val Ala Glu Arg 340 345 350 Phe Ala Glu Arg Gly Ala Ala Leu Val Thr Glu Val Pro Asp Leu Thr 355 360 365 Pro Asp Arg Leu Arg Asp Gln Leu Arg Arg Leu Ile Ala Glu Pro Ser 370 375 380 Phe Lys Ala Ala Ala Glu Gln Ile Gln Lys Glu Tyr Asp Ala Leu Pro 385 390 395 400 Ser Leu Thr Glu Thr Val Gly Glu Leu Val Arg Val Ala Glu Arg Gly 405 410 415 Arg Ser Leu 5 2260 PRT Streptomyces halstedii sp.HC-34 5 Val Glu Asn Glu Lys Lys Leu Leu Asp Tyr Leu Lys Arg Ala Thr Thr 1 5 10 15 Asp Leu Arg Glu Ala Arg Arg Arg Leu Arg Glu Met Glu Glu Lys Asp 20 25 30 Gln Glu Pro Ile Ala Ile Val Gly Ile Gly Cys Arg Phe Pro Arg Gly 35 40 45 Val Glu Ser Ala Glu Gln Leu Trp Asp Leu Val Ala Asp Gly Gly Glu 50 55 60 Ala Leu Thr Pro Phe Pro Glu Asp Arg Gly Trp Asp Thr Asp Ser Leu 65 70 75 80 Tyr His Pro Asp Pro Glu His Leu Gly Thr Ser Tyr Thr Asn Val Gly 85 90 95 Ala Phe Leu His Asp Ala Ala Glu Phe Asp Pro Gly Phe Phe Gly Ile 100 105 110 Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Leu Leu 115 120 125 Glu Thr Ser Trp Glu Ala Met Glu Arg Ala Gly Ile Asp Pro Ala Gly 130 135 140 Leu Arg Gly Ser Arg Thr Gly Val Phe Thr Gly Leu Met Tyr Phe Asp 145 150 155 160 Tyr Gly Ser Arg Val His Ser Ala Pro Glu Asp Ile Glu Gly Tyr Leu 165 170 175 Gly Asn Gly Ser Ala Gly Ser Ile Ala Ser Gly Arg Val Ala Tyr Thr 180 185 190 Phe Gly Phe Glu Gly Pro Ala Val Thr Leu Asp Thr Ala Cys Ser Ser 195 200 205 Ser Leu Val Ala Ile His Leu Ala Ala Gln Ser Leu Arg Lys Gly Glu 210 215 220 Cys Thr Leu Ala Leu Ala Gly Gly Ala Ser Val Met Ser Thr Pro Asp 225 230 235 240 Ile Phe Val Asp Phe Ser Arg Gln Arg Gly Leu Ser Ala Asp Gly Arg 245 250 255 Cys Lys Ala Phe Ser Ser Asp Ala Asp Gly Thr Gly Trp Gly Glu Gly 260 265 270 Val Gly Val Leu Leu Leu Glu Arg Leu Ser Asp Ala Arg Lys Asn Gly 275 280 285 His Arg Ile Leu Gly Leu Val Arg Gly Ser Ala Val Asn Gln Asp Gly 290 295 300 Ala Ser Ser Gly Leu Thr Ala Pro Asn Gly Pro Ser Gln Gln Arg Val 305 310 315 320 Ile Arg Gln Ala Leu Ala Asn Ala Gly Leu Ser Ala Ala Glu Val Asp 325 330 335 Ala Val Glu Ala His Gly Thr Gly Thr Lys Leu Gly Asp Pro Ile Glu 340 345 350 Ala Gln Ala Leu Leu Ala Thr Tyr Gly Gln Glu Arg Glu Glu Gly Arg 355 360 365 Pro Leu Trp Leu Gly Ser Ile Lys Ser Asn Val Gly His Thr Gln Ala 370 375 380 Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Leu Ala Met Arg Ala 385 390 395 400 Gly Val Leu Pro Lys Thr Leu His Val Ser Glu Pro Ser Pro His Val 405 410 415 Asp Trp Ser Ala Gly Ala Val Glu Leu Leu Thr Glu Thr Arg Asp Trp 420 425 430 Pro Glu Thr Gly Arg Pro Arg Arg Ala Gly Val Ser Ser Phe Gly Ile 435 440 445 Ser Gly Thr Asn Ala His Val Ile Val Glu Gln Ala Pro Met Asp Glu 450 455 460 Ala Met Asp Glu Val Ala Gly Glu Arg Glu Thr Pro Ala Ala Gly Ser 465 470 475 480 Asp Arg Thr Val Pro Trp Val Ile Ser Ala Lys Ser Ala Asp Ala Leu 485 490 495 Arg Ala Gln Ala Gly Arg Leu Ser Thr Phe Leu Ala Gly Thr Glu Gly 500 505 510 Thr Leu Thr Thr Gly Ile Ser Ser Glu Thr Ser Val Ala Ala Val Ser 515 520 525 Ala Asp Ala Ser Ala Val Gly Trp Ser Leu Val Arg Gly Arg Ser Val 530 535 540 Phe Ala His Arg Ala Val Val Val Gly Gly Glu Trp Asp Ala Leu Leu 545 550 555 560 Ala Ser Ile Gly Glu Leu Ala Asp Gly Ala Glu Asp Gly Ser Gly Ala 565 570 575 Ala Ser Gly Ser Val Val Ser Gly Val Ala Asp Val Ser Gly Arg Arg 580 585 590 Val Phe Val Phe Pro Gly Gln Gly Ser Gln Trp Val Gly Met Ala Gln 595 600 605 Gly Leu Leu Asp Ser Ser Val Met Phe Thr Glu Arg Met Thr Glu Cys 610 615 620 Ala Ala Ala Leu Asp Pro Leu Val Glu Trp Ser Leu Leu Asp Val Val 625 630 635 640 Arg Gly Val Glu Gly Ala Ala Ser Leu Glu Arg Val Asp Val Val Gln 645 650 655 Pro Val Leu Trp Ala Val Met Val Ser Leu Ala Ser Val Trp Arg Ser 660 665 670 Val Gly Val Val Pro Asp Ala Val Val Gly His Ser Gln Gly Glu Ile 675 680 685 Ala Ala Ala Val Val Gly Gly Trp Leu Ser Leu Val Asp Gly Ala Arg 690 695 700 Val Val Ala Leu Arg Ser Leu Ala Ile Arg Glu Val Leu Ala Gly Gly 705 710 715 720 Gly Gly Met Val Ala Val Gln Ala Ala Glu Asp Glu Val Ala Gly Trp 725 730 735 Leu Glu Gly Val Glu Gly Val Gly Ile Ala Ala Val Asn Gly Pro Arg 740 745 750 Ser Val Val Ile Ser Gly Thr Arg Ala Gly Leu Asp Ala Cys Val Glu 755 760 765 Leu Trp Ser Gly Arg Gly Thr Trp Val Lys Arg Val Pro Val Asp Tyr 770 775 780 Ala Ser His Ser Ala Glu Val Glu Arg Val Arg Glu Arg Val Leu Ala 785 790 795 800 Asp Leu Ala Ser Val Thr Gly Leu Ser Gly Ser Val Pro Met Leu Ser 805 810 815 Thr Met Thr Gly Asp Trp Ile Val Glu Gly Gln Val Gly Ala Gly Tyr 820 825 830 Trp Val Glu Asn Leu Arg Arg Pro Val Leu Phe Ala Asp Ala Thr Arg 835 840 845 Arg Leu Ala Ser Glu Gly Phe Gly Ala Phe Val Glu Val Ser Ala His 850 855 860 Pro Val Leu Val Met Gly Ile Glu Glu Thr Ile Glu Ala Leu Arg Ser 865 870 875 880 Gly Ala Ala Asp Gly Ala Lys Ser Gly Ala Gly Glu Glu Ser Ser Ser 885 890 895 Ala Val Val Ala Val Gly Thr Leu Arg Arg Gly Glu Gly Gly Trp Asp 900 905 910 Gln Phe Leu Arg Ser Leu Ala Gly Leu Phe Val Arg Gly Ala Val Thr 915 920 925 Pro Asp Trp Glu Ser Leu Leu Gly Gly Val Arg Pro Arg Val Asp Leu 930 935 940 Pro Thr Tyr Ala Phe Gln Arg Glu Arg Leu Trp Leu Asp Ala Gly Val 945 950 955 960 Val Ala Gly Asp Val Ser Gly Leu Gly Gln Val Val Val Gly His Pro 965 970 975 Leu Leu Gly Ala Gly Val Gly Val Ala Gly Glu Gly Gly Gly Val Leu 980 985 990 Phe Thr Gly Arg Leu Gly Leu Gly Ser His Pro Trp Leu Gly Asp His 995 1000 1005 Ala Val Ser Gly Val Val Leu Leu Pro Gly Ala Ala Phe Val Glu 1010 1015 1020 Leu Val Val Arg Ala Gly Asp Glu Val Gly Cys Gly Arg Leu Glu 1025 1030 1035 Glu Leu Thr Leu Ala Ala Pro Leu Val Val Pro Glu Arg Gly Ser 1040 1045 1050 Val Arg Ile Gln Val Val Val Gly Ala Gly Asp Gly Ser Gly Ala 1055 1060 1065 Arg Ser Val Gly Val Trp Ser Ser Val Gly Asp Glu Gly Val Gly 1070 1075 1080 Gly Glu Trp Val Cys His Ala Ser Gly Leu Leu Thr Ala Asp Val 1085 1090 1095 Gly Val Ala Pro Val Leu Gly Gly Val Trp Pro Pro Val Gly Gly 1100 1105 1110 Val Ala Val Asp Val Ser Gly Val Tyr Glu Gly Leu Ala Leu Glu 1115 1120 1125 Gly Tyr Glu Tyr Gly Ser Val Phe Arg Gly Leu Arg Ser Val Trp 1130 1135 1140 Arg Arg Gly Asp Glu Val Phe Ala Glu Val Ala Leu Gly Glu Gly 1145 1150 1155 Val Gly Val Glu Gly Phe Gly Leu His Pro Ala Leu Leu Asp Ala 1160 1165 1170 Ala Leu Gln Ala Ala Gly Phe Gly Ser Phe Val Pro Glu Ser Glu 1175 1180 1185 Ala Gly Ser Glu Ala Gly Ser Gly Gly Val Arg Leu Pro Phe Ser 1190 1195 1200 Trp Ser Gly Val Ser Leu Phe Ala Ser Gly Ala Ser Val Gly Arg 1205 1210 1215 Val Arg Leu Trp Pro Val Gly Gly Asp Gly Phe Gly Val Glu Leu 1220 1225 1230 Phe Asp Gly Val Gly Met Pro Val Ala Arg Val Asp Ala Leu Val 1235 1240 1245 Thr Arg Glu Ile Ser Ala Gly Gln Leu Gly Ala Ala Ala Gly Ala 1250 1255 1260 Gly Ser Leu Val Gly Gly Glu Ser Leu Phe Arg Val Glu Trp Ala 1265 1270 1275 Pro Val Ser Gly Val Ala Pro Ala Ser Ala Gly Val Gly Gly Cys 1280 1285 1290 Val Val Val Gly Ala Gly Ser Val Leu Ser Gly Phe Gly Glu Val 1295 1300 1305 Val Pro Asp Leu Ala Ala Val Ser Ala Gly Ser Ala Ala Val Pro 1310 1315 1320 Gly Trp Val Leu Val Asp Val Asp Ala Trp Leu Gly Ala Asp Leu 1325 1330 1335 Ala Val Gly Val Val Ser Gly Glu Gly Val Pro Val Val Ala Arg 1340 1345 1350 Gly Val Val Ala Arg Val Leu Gly Leu Val Arg Glu Trp Leu Gly 1355 1360 1365 Asp Glu Arg Trp Val Ser Ser Arg Leu Val Trp Val Thr Arg Gly 1370 1375 1380 Ala Val Gly Ala Arg Val Leu Asp Glu Val Ser Gly Val Val Ser 1385 1390 1395 Ser Gly Leu Trp Gly Leu Val Arg Ala Ala Gln Ser Glu His Pro 1400 1405 1410 Asp Arg Phe Ala Leu Leu Asp Leu Asp Ser Ala Thr Ala Val Asp 1415 1420 1425 Ala Val Arg Asp Gly Val Leu Gly Leu Leu Ala Ala Gly Glu Pro 1430 1435 1440 Gln Leu Val Val Arg Glu Gly Glu Val Leu Ala Ala Arg Leu Thr 1445 1450 1455 Pro Ala His Thr Thr Asp Ala Leu Ile Pro Leu Ala Asp His Ala 1460 1465 1470 Pro Trp Arg Leu Ala Lys Asp Pro Gly Gly Ser Leu Asp Ala Leu 1475 1480 1485 Thr Val Val Pro Ala Pro Asp Val Leu Glu Pro Leu Thr Glu Gly 1490 1495 1500 Gln Val Arg Ile Ala Val Arg Ala Ala Gly Val Asn Phe Arg Asp 1505 1510 1515 Val Leu Met Ala Leu Gly Met Val Pro Ala Arg Gly Thr Gln Leu 1520 1525 1530 Gly Gly Glu Ala Ala Gly Val Val Thr Ala Val Gly Pro Gly Val 1535 1540 1545 Thr Gly Ile Ala Val Gly Asp Arg Val Met Gly Val Phe Asp Gly 1550 1555 1560 Pro Phe Gly Pro Val Ala Val Ala Asp Arg Arg Met Val Ser Arg 1565 1570 1575 Ile Pro Asp Ala Trp Ser Tyr Thr Glu Ala Ala Thr Ile Pro Leu 1580 1585 1590 Val Tyr Leu Thr Ala Tyr Tyr Gly Leu Val Asp Leu Ala Ala Leu 1595 1600 1605 Gln Gln Gly Gln Arg Ile Leu Val His Ala Ala Thr Gly Gly Val 1610 1615 1620 Gly Met Ala Ala Val Gln Leu Ala Arg His Phe Gly Ala Glu Val 1625 1630 1635 Tyr Gly Thr Ala Ser Pro Gly Lys Trp Asp Thr Leu Arg Ala Met 1640 1645 1650 Gly Phe Asp Glu Ala His Met Ala Ser Ser Arg Ser Leu Asp Phe 1655 1660 1665 Glu Asp His Phe Trp Gln Thr Thr Gly Gly Glu Gly Phe Asp Val 1670 1675 1680 Val Leu Asn Ser Leu Ala Gln Glu Tyr Val Asp Ala Ser Leu Arg 1685 1690 1695 Leu Gln Pro Arg Gly Gly Arg Phe Leu Glu Met Gly Lys Thr Asp 1700 1705 1710 Ile Arg Asp Ala Asp Glu Val Ala Ala Ala His Glu Gly Val Arg 1715 1720 1725 Tyr Glu Ala Tyr Asp Leu Thr Val Phe Thr Ser Val Asp Gly Pro 1730 1735 1740 Gly Ala Ile Pro Glu Arg Ile Gln Glu Met Leu Ser Glu Leu Leu 1745 1750 1755 Ala Leu Phe Asp Lys Gly Val Leu Thr Pro Leu Pro Val Thr Thr 1760 1765 1770 Trp Asp Val Arg Arg Ala Ser Ala Ala Leu Arg His Met Ser Gln 1775 1780 1785 Ala Arg His Thr Gly Lys Ile Ala Leu Thr Val Pro Arg Pro Leu 1790 1795 1800 Asp Gln Asp Gly Thr Val Leu Val Thr Gly Gly Thr Gly Val Leu 1805 1810 1815 Gly Ser Leu Leu Ala Arg His Leu Val Thr Glu His Gly Val Arg 1820 1825 1830 Asn Leu Leu Leu Val Ser Arg Arg Gly Gly Asp Ala Pro Gly Ala 1835 1840 1845 Ala Glu Leu Val Ala Glu Leu Thr Ala Ala Gly Ala Glu Val Ser 1850 1855 1860 Val Val Ala Cys Asp Thr Ala Asp Arg Ala Ala Leu Glu Lys Leu 1865 1870 1875 Leu Ala Ser Val Pro Gly Asp Ala Pro Leu Thr Gly Val Phe His 1880 1885 1890 Thr Ala Gly Val Leu Asp Asp Gly Ile Val Glu Ala Met Thr Pro 1895 1900 1905 Glu Arg Val Asp Ala Val Met Arg Pro Lys Val Asp Ala Ala Trp 1910 1915 1920 His Leu His Glu Leu Thr Glu Gly Leu Asp Leu Ala Ala Phe Val 1925 1930 1935 Leu Tyr Ser Ser Ala Ala Gly Val Ser Gly Asp Ala Gly Gln Ser 1940 1945 1950 Asn Tyr Ala Ala Ala Asn Val Phe Leu Asp Ala Leu Ala Gln Arg 1955 1960 1965 Arg Arg Ala Ala Gly Leu Pro Gly Gln Ser Leu Ala Trp Gly Leu 1970 1975 1980 Trp Asp Asp Arg Ser Glu Met Thr Gly His Leu Gly Asp Ala Glu 1985 1990 1995 Ile Ala Arg Met Thr Glu Ala Gly Val Leu Gly Phe Thr Ala Ala 2000 2005 2010 Asp Gly Leu Ala Ala Leu Asp Arg Ala Ala Met Tyr Asp Asp Ala 2015 2020 2025 Val Leu Val Pro Met Lys Leu Asp Thr Ala Thr Leu Gly Ala Gly 2030 2035 2040 Ser Ser Pro Val Pro His Leu Phe Arg Gly Leu Val Arg Thr Pro 2045 2050 2055 Val Val Arg Arg Ala Val Ala Gly Asn Thr Gly Gly Asp Ser Gly 2060 2065 2070 Gly Gly Leu Glu Gln Arg Leu Ala Ala Leu Thr Ala Ala Glu Arg 2075 2080 2085 Thr Glu Thr Val Leu Glu Leu Val Arg Glu Arg Val Ala Ala Val 2090 2095 2100 Leu Gly His Ala Ser Ala Asp Ala Ile Asp Pro Ala Arg Ala Phe 2105 2110 2115 Lys Glu Ile Gly Phe Asp Ser Leu Thr Ala Val Glu Leu Arg Asn 2120 2125 2130 Arg Leu Asn Ala Ala Thr Gly Leu Arg Leu Pro Ala Thr Leu Val 2135 2140 2145 Phe Asp Tyr Pro Thr Pro Thr Val Leu Ser Gln Tyr Leu Leu Ala 2150 2155 2160 Glu Leu Ala Pro Gly Leu Pro Ala Glu Asp Pro Val Gly Thr Arg 2165 2170 2175 Leu Leu Glu Gln Ile Ala Arg Ile Glu Ala Val Leu Ser Glu Val 2180 2185 2190 Ser Glu Val Thr Asp Glu Thr Ser Ser Leu Ser Asp Met Asp Ala 2195 2200 2205 Asp Ala Arg Ser Gly Ile Thr Ala Arg Leu Asn Asp Ile Leu Thr 2210 2215 2220 Ala Trp Asn Arg Ala Gln Arg Ala Pro Gly His Asp Ala Val Ala 2225 2230 2235 Ala Glu Leu Asp Asp Ala Ser Asp Asp Glu Ile Phe Asp Phe Ile 2240 2245 2250 Asp Ser Thr Phe Gly Lys Ser 2255 2260 6 3362 PRT Streptomyces halstedii sp.HC-34 6 Met Ala Asn Glu Ala Lys Leu Arg Glu Tyr Leu Lys Arg Val Thr Thr 1 5 10 15 Asp Leu His Glu Thr Asn Glu Arg Leu Arg Glu Val Glu Gly Arg Ala 20 25 30 Asn Glu Pro Ile Ala Ile Val Gly Met Ser Cys Arg Phe Pro Gly Gly 35 40 45 Val Glu Ser Pro Glu Gln Leu Trp Glu Leu Phe Arg Thr Gly Thr Asp 50 55 60 Ala Ile Gly Glu Phe Pro Glu Gly Arg Gly Trp Asp Val Glu Gly Leu 65 70 75 80 Tyr His Pro Asp Pro Asp His Ala Gly Thr Ser Tyr Thr Arg Glu Gly 85 90 95 Gly Phe Val His Gly Ala Glu Arg Phe Asp Pro Ser Leu Phe Gly Ile 100 105 110 Ser Pro Arg Glu Ala Val Ser Met Asp Pro Gln Gln Arg Leu Leu Leu 115 120 125 Glu Thr Ser Trp Glu Ala Leu Glu Ala Ser Gly Leu Asp Pro Leu Arg 130 135 140 Leu Lys Gly Ser Arg Thr Gly Val Phe Val Gly Val Met Ser Ser Asp 145 150 155 160 Tyr Gly Ile Gln Lys Gly Ser Ala Pro Asp Gly Val Glu Gly Phe Leu 165 170 175 Ser Thr Gly Thr His Ser Ser Ile Val Ser Gly Arg Val Ser Tyr Val 180 185 190 Leu Gly Leu Glu Gly Pro Ala Val Ser Val Asp Thr Ala Cys Ser Ser 195 200 205 Ser Leu Val Ala Leu His Ser Ala Ala His Ala Leu Arg Gln Gly Glu 210 215 220 Cys Ser Leu Ala Leu Ala Gly Gly Val Thr Ile Met Ser Thr Pro Glu 225 230 235 240 Arg Phe Val Glu Phe Ser Arg Gln Arg Ala Leu Ser Ala Asp Gly Arg 245 250 255 Cys Lys Ala Phe Ser Ala Ser Ala Asp Gly Thr Gly Trp Ser Glu Gly 260 265 270 Val Gly Met Leu Val Leu Glu Arg Leu Ser Asp Ala Arg Lys Asn Gly 275 280 285 His Arg Val Leu Ala Val Ile Arg Gly Ser Ala Leu Asn Gln Asp Gly 290 295 300 Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ser Gln Gln Arg Val 305 310 315 320 Ile Arg Gln Ala Leu Ala Ser Ala Gly Leu Thr Ala Ala Glu Val Asp 325 330 335 Ala Val Glu Ala His Gly Thr Gly Thr Thr Leu Gly Asp Pro Ile Glu 340 345 350 Ala Gln Ala Leu Leu Ala Thr Tyr Gly Lys Glu Arg Glu Asp Gly Arg 355 360 365 Pro Leu Leu Leu Gly Ser Ser Lys Ser Asn Leu Gly His Thr Gln Ala 370 375 380 Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Leu Ala Met Arg Ala 385 390 395 400 Gly Val Leu Pro Lys Thr Leu His Val Ser Glu Pro Ser Pro His Val 405 410 415 Asp Trp Ser Ala Gly Ala Val Glu Leu Leu Thr Glu Ala Arg Glu Trp 420 425 430 Pro Glu Thr Gly Arg Pro Arg Arg Ala Gly Val Ser Ser Phe Gly Phe 435 440 445 Ser Gly Thr Asn Ala His Val Ile Ile Glu Glu Ala Ser Glu Phe Glu 450 455 460 Pro Ser Ala Val Glu Pro Leu Ala Gly Ser Gly Val Thr Pro Pro Trp 465 470 475 480 Val Leu Ser Ala Arg Ser Ala Asp Ala Leu Arg Gly Gln Ala Glu Arg 485 490 495 Leu Leu Ser Phe Val Ser Ala Ala Gly Asp Val Ser Val Val Asp Val 500 505 510 Ala Tyr Ser Leu Gly Val Ser Arg Ala Gly Leu Glu His Arg Gly Val 515 520 525 Val Val Gly Glu Ser Arg Ala Glu Leu Leu Ala Ala Leu Glu Ser Leu 530 535 540 Ala Ser Gly Val Glu Ser Pro Gly Val Val Thr Gly Arg Val Ala Glu 545 550 555 560 Gly Arg Leu Ala Phe Leu Phe Thr Gly Gln Gly Ala Gln Arg Val Gly 565 570 575 Met Gly Arg Glu Leu Ala Ala Ala Phe Pro Leu Phe Ala Ala Ser Leu 580 585 590 Glu Glu Thr Cys Gly Leu Leu Glu Arg Ala Gly Val Ala Val Arg Glu 595 600 605 Val Leu Phe Ala Glu Glu Gly Ser Ala Glu Ala Ala Leu Leu Thr Arg 610 615 620 Thr Val Tyr Ala Gln Ala Ala Leu Phe Ala Val Glu Val Ala Leu Phe 625 630 635 640 Arg Leu Val Glu Ser Phe Gly Val Val Pro Asp Phe Val Ala Gly His 645 650 655 Ser Val Gly Glu Ile Ala Ala Ala His Val Ala Gly Val Phe Ser Leu 660 665 670 Glu Asp Ala Val Ser Leu Val Ala Ala Arg Gly Arg Leu Met Asp Ala 675 680 685 Leu Pro Glu Gly Gly Ala Met Val Ala Val Gln Ala Thr Glu Glu Asp 690 695 700 Val Leu Ala Leu Leu Glu Gly Val Glu Asp Ala Ser Ile Ala Ala Ile 705 710 715 720 Asn Gly Pro Asp Ala Val Val Val Ser Gly Thr Glu Ala Gly Val Ala 725 730 735 Arg Val Val Asp Val Leu Arg Glu Arg Gly Ala Lys Thr Lys Arg Leu 740 745 750 Val Val Ser His Ala Phe His Ser Pro Leu Met Glu Pro Met Leu Ala 755 760 765 Glu Phe Ala Thr Val Val Glu Gly Leu Ser Phe Ala Ala Pro Thr Ile 770 775 780 Pro Val Val Ser Asn Val Ser Gly Ala Val Ala Asp Ala Glu Leu Ser 785 790 795 800 Ser Pro Gly Tyr Trp Val Arg His Val Arg Glu Ala Val Arg Phe Gly 805 810 815 Ala Gly Val Glu Thr Leu Leu Gly Ala Gly Val Ser Ser Phe Leu Glu 820 825 830 Ile Gly Pro Asp Gly Val Leu Ser Gly Met Ala Arg Thr Ser Val Pro 835 840 845 Glu Gly Ala Asp Val Glu Cys Ala Pro Leu Met Arg Arg Gly Arg Gly 850 855 860 Glu Val Arg Glu Phe Leu Thr Gly Leu Ser Arg Met Val Val Arg Gly 865 870 875 880 Val Pro Val Asp Trp Gln Ser Leu Val Glu Gly Gly Arg Leu Ala Gly 885 890 895 Leu Pro Thr Tyr Ala Phe Gln Arg Glu Arg Phe Trp Leu Asp Val Pro 900 905 910 Ser Ala Val Gly Asp Val Ala Thr Ala Gly Leu Ala Pro Ser Gly His 915 920 925 Pro Leu Leu Gly Ala Val Met Arg Arg Ala Asp Val Asp Gly Val Val 930 935 940 Phe Thr Gly Arg Trp Ser Leu Arg Ser His Pro Trp Leu Gly Glu His 945 950 955 960 Arg Val Gly Ser Ser Val Val Phe Pro Gly Thr Gly Phe Val Glu Leu 965 970 975 Leu Met Arg Ala Gly Asp Glu Val Gly Cys Gly Arg Ile Glu Glu Leu 980 985 990 Asn Gln Glu Thr Pro Leu Val Val Pro Glu Arg Gly Ala Leu Gln Leu 995 1000 1005 Gln Val Val Val Gly Ala Pro Glu Glu Thr Gly Leu Arg Gly Val 1010 1015 1020 Gly Val Tyr Ser Arg Ala Glu Asp Ala Asp Ala Asp Val Pro Trp 1025 1030 1035 Thr Arg His Ala Ser Gly Leu Leu Ser Pro Ala Val Val Pro Ala 1040 1045 1050 Asp Phe Glu Leu Thr Gln Trp Pro Pro Ala Gly Ala Glu Ala Leu 1055 1060 1065 Asn Val Glu Asp Thr Tyr Gln Arg Leu Ala Asp Ala Gly Leu Val 1070 1075 1080 Tyr Gly Glu Arg Phe Gln Gly Leu Lys Ser Gly Trp Ile Lys Gly 1085 1090 1095 Glu Asp Ile Tyr Ala Glu Ile Ala Leu Pro Glu His Ala Val Ala 1100 1105 1110 Glu Ala Ala Glu Tyr Thr Leu His Pro Ala Ala Leu Asp Ala Ala 1115 1120 1125 Leu Gln Ala Ser Gly Leu Asn Asp Pro Pro Glu Val Gln Ala Thr 1130 1135 1140 Ala Tyr Val Pro Phe Ser Trp Ser Gly Val Ser Leu Phe Ala Ser 1145 1150 1155 Gly Ala Ser Val Leu Arg Val Cys Val Arg His Val Ala Arg Asp 1160 1165 1170 Arg Val Ser Leu Leu Val Ala Asp Gly Val Gly Val Pro Val Ala 1175 1180 1185 Val Val Glu Ser Leu Val Leu Arg Ala Ile Ser Ala Gly Ala Val 1190 1195 1200 Ala Val Ala Gly Val Gly Ser Gly Val Gly Gly Gly Leu Phe Glu 1205 1210 1215 Val Val Trp Ser Pro Val Val Gly Val Arg Gly Val Asp Val Ser 1220 1225 1230 Gly Val Val Val Leu Glu Ala Gly Val Gly Val Gly Gly Asp Gly 1235 1240 1245 Val Ser Val Val Gly Gly Val Leu Glu Gly Leu Gln Gly Val Leu 1250 1255 1260 Gly Gly Gly Ser Gly Ser Arg Val Val Val Val Thr Arg Gly Ala 1265 1270 1275 Val Gly Ser Gly Gly Val Val Asp Val Ser Gly Ala Gly Val Trp 1280 1285 1290 Gly Leu Val Arg Ser Val Gln Ala Glu His Pro Gly Arg Leu Val 1295 1300 1305 Leu Val Asp Val Gly Val Glu Gly Asp Val Gly Val Gly Val Gly 1310 1315 1320 Leu Ala Leu Gly Ser Gly Glu Glu Gln Val Val Val Arg Gly Gly 1325 1330 1335 Glu Val Phe Val Pro Arg Leu Ala Arg Val Gly Ala Val Ala Ala 1340 1345 1350 Asp Ala Gly Val Asp Gly Ala Glu Ile Ala Gly Gly Leu Gly Asp 1355 1360 1365 Gly Val Val Leu Val Thr Gly Gly Thr Gly Gly Leu Gly Ala Leu 1370 1375 1380 Val Ala Arg His Val Val Val Glu Arg Gly Val Arg Arg Leu Val 1385 1390 1395 Leu Val Ser Arg Arg Gly Leu Gly Ala Pro Gly Ala Val Gly Leu 1400 1405 1410 Val Ala Glu Leu Glu Gly Leu Gly Ala Val Val Glu Val Val Ala 1415 1420 1425 Cys Asp Val Ser Asp Arg Val Ala Leu Ala Gly Val Val Gly Gly 1430 1435 1440 Ile Gly Ser Asp Leu Ser Ala Val Val His Thr Ala Gly Val Val 1445 1450 1455 Asp Asp Gly Val Val Glu Ser Met Ser Val Gly Arg Val Ala Ser 1460 1465 1470 Val Phe Gly Pro Lys Ala Asp Ala Ala Trp Phe Leu His Glu Leu 1475 1480 1485 Thr Arg Asp Met Gly Leu Ser Ala Phe Val Leu Phe Ser Ser Met 1490 1495 1500 Ala Gly Thr Val Gly Gly Gly Gly Gln Ser Asn Tyr Ala Ala Ala 1505 1510 1515 Asn Ala Tyr Leu Asp Gly Leu Ala Glu Tyr Arg Arg Gly Leu Gly 1520 1525 1530 Leu Ala Ala Thr Ser Leu Ala Trp Gly Leu Trp Glu Glu Ser Thr 1535 1540 1545 Gly Met Gly Ser Arg Leu Thr Asp Ala Asp Leu Asp Arg Met Ser 1550 1555 1560 Arg Ser Gly Ile Arg Thr Leu Ser Ile Glu Asp Gly Leu Ala Leu 1565 1570 1575 Phe Asp Ala Ala Leu Ala Ala Asp Arg Pro Thr Val Met Pro Ala 1580 1585 1590 His Phe Asp Ile Pro Ala Leu Arg Gly Gln Gly Glu Ser Leu Ala 1595 1600 1605 Pro Val Phe Arg Thr Leu Ala Gly Pro Pro Ala Arg Arg Ser Ala 1610 1615 1620 Ala Val Thr Pro Arg Asp Ile Ala Ala Ala Thr Glu Ser Ser Leu 1625 1630 1635 Thr Asp Arg Leu Ala Gly Leu Asp Ala Glu Gly Arg Arg Ala Leu 1640 1645 1650 Val Leu Gly Val Val Arg Ala Gln Val Ala Gln Val Leu Ala Tyr 1655 1660 1665 Ala Ser Pro Asp Leu Val Glu Pro Glu Arg Ala Phe Gln Asp Leu 1670 1675 1680 Gly Phe Asp Ser Leu Thr Ala Val Glu Leu Arg Asn Gly Leu Thr 1685 1690 1695 Ala Ile Ala Gly Val Arg Leu Pro Ala Thr Leu Val Phe Asp Tyr 1700 1705 1710 Pro Ser Thr Asp Ile Leu Thr Asp Phe Leu Leu Ala Glu Leu Ser 1715 1720 1725 Asp Glu Ile Pro Ala Ala Val Ala Thr Leu Pro Ala Met Gly His 1730 1735 1740 Val Val Asp Asp Asp Pro Ile Ala Val Ile Gly Met Gly Cys Arg 1745 1750 1755 Tyr Pro Gly Gly Val Glu Ser Pro Glu Glu Leu Trp Lys Leu Met 1760 1765 1770 Ala Glu Gly Arg Asp Ala Ile Ser Glu Phe Pro Thr Asp Arg Gly 1775 1780 1785 Trp Asp Leu Asp Ala Ile Tyr His Pro Asp Pro Met His Thr Gly 1790 1795 1800 Thr Ser Tyr Thr Arg Glu Gly Gly Phe Ile His Asn Ala Gly Asp 1805 1810 1815 Phe Asp Ala Ala Phe Phe Gly Ile Ser Pro Arg Glu Ala Met Glu 1820 1825 1830 Thr Asp Pro Gln Gln Arg Leu Leu Leu Glu Thr Ser Trp Glu Ala 1835 1840 1845 Phe Glu Gln Ala Gly Ile Val Pro Thr Asp Leu Lys Gly Thr Gln 1850 1855 1860 Thr Gly Val Phe Ala Gly Val Met Tyr His Asp Tyr Ala Gly Asn 1865 1870 1875 Ile Gly Ser Gly Ser Ile Val Thr Gly Arg Val Ala Tyr Thr Leu 1880 1885 1890 Gly Leu Glu Gly Pro Ala Val Ser Ile Asp Thr Ala Cys Ser Ser 1895 1900 1905 Ser Leu Val Ala Ile His Leu Ala Ala Gln Ser Leu Arg Gln Gly 1910 1915 1920 Glu Cys Ser Met Ala Ile Ala Gly Gly Val Ala Val Met Ala Thr 1925 1930 1935 Pro Glu Ser Phe Ile Glu Phe Ser Arg Gln Arg Ala Leu Ser Gln 1940 1945 1950 Asn Gly Arg Cys Arg Ala Phe Ser Ser Asp Ala Asp Gly Thr Ala 1955 1960 1965 Trp Gly Glu Gly Val Gly Val Leu Ile Leu Glu Arg Leu Ser Asp 1970 1975 1980 Ala Arg Lys Asn Gly His Glu Val Leu Ala Val Ile Arg Gly Ser 1985 1990 1995 Ala Leu Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn 2000 2005 2010 Gly Pro Ser Gln Gln Arg Val Ile Arg Gln Ala Leu Ala Asn Ser 2015 2020 2025 Gly Leu Ser Ala Ala Glu Val Asp Ala Val Glu Ala His Gly Thr 2030 2035 2040 Gly Thr Thr Leu Gly Asp Pro Ile Glu Ala Gln Ala Leu Leu Ala 2045 2050 2055 Thr Tyr Gly Lys Glu Arg Asp Ala Asp Gln Pro Leu Trp Leu Gly 2060 2065 2070 Ser Ser Lys Ser Asn Phe Gly His Thr Lys Ala Ala Ala Gly Val 2075 2080 2085 Ala Gly Val Ile Lys Met Val Met Ala Ile Arg Asn Gly Val Leu 2090 2095 2100 Pro Lys Thr Leu His Val Thr Glu Pro Ser Pro His Val Asp Trp 2105 2110 2115 Ser Ala Gly Ala Val Glu Leu Leu Ala Glu Ala Arg Glu Trp Pro 2120 2125 2130 Glu Thr Gly Arg Pro Arg Arg Ala Gly Val Ser Ser Phe Gly Ile 2135 2140 2145 Ser Gly Thr Asn Ala His Val Ile Val Glu Gln Ala Pro Thr Asp 2150 2155 2160 Gln Ala Ala Thr Lys Pro Lys Ala Ala Asp Ala Val Pro Gly Leu 2165 2170 2175 Pro Val Pro Trp Val Val Ser Ala Lys Asn Pro Glu Ala Leu Arg 2180 2185 2190 Ala Gln Ala Gly Arg Leu Gly Ser Phe Leu Gly Glu Thr Gly Val 2195 2200 2205 Val Asp Val Pro Ala Val Gly Trp Ser Leu Val Arg Gly Arg Ser 2210 2215 2220 Val Phe Ala His Arg Ala Val Val Val Gly Gly Glu Trp Asp Ala 2225 2230 2235 Leu Leu Ala Ser Ile Gly Glu Leu Ala Asp Gly Ala Glu Asp Gly 2240 2245 2250 Ser Gly Ala Ala Ser Gly Ser Val Val Ser Gly Val Ala Asp Val 2255 2260 2265 Ser Gly Arg Arg Val Phe Val Phe Pro Gly Gln Gly Ser Gln Trp 2270 2275 2280 Val Gly Met Ala Gln Gly Leu Leu Asp Ser Ser Val Val Phe Thr 2285 2290 2295 Glu Arg Met Thr Glu Cys Ala Ala Ala Leu Asp Pro Leu Val Glu 2300 2305 2310 Trp Ser Leu Leu Asp Val Val Arg Gly Val Glu Gly Ala Ala Ser 2315 2320 2325 Leu Glu Arg Val Asp Val Val Gln Pro Val Leu Trp Ala Val Met 2330 2335 2340 Val Ser Leu Ala Ser Val Trp Arg Ser Val Gly Val Val Pro Asp 2345 2350 2355 Ala Val Val Gly His Ser Gln Gly Glu Ile Ala Ala Ala Val Val 2360 2365 2370 Gly Gly Trp Leu Ser Leu Val Asp Gly Ala Arg Val Val Ala Leu 2375 2380 2385 Arg Ser Leu Ala Ile Arg Glu Val Leu Ala Gly Gly Gly Gly Met 2390 2395 2400 Val Ala Val Gln Ala Ala Glu Asp Glu Val Ala Gly Trp Leu Glu 2405 2410 2415 Gly Val Glu Gly Val Gly Ile Ala Ala Val Asn Gly Pro Arg Ser 2420 2425 2430 Val Val Ile Ser Gly Thr Arg Ala Gly Leu Asp Ala Cys Val Glu 2435 2440 2445 Leu Trp Ser Gly Arg Gly Thr Trp Val Lys Arg Val Pro Val Asp 2450 2455 2460 Tyr Ala Ser His Ser Ala Glu Val Glu Arg Val Arg Glu Arg Val 2465 2470 2475 Leu Ala Asp Leu Ala Ser Val Thr Gly Leu Ser Gly Ser Val Pro 2480 2485 2490 Met Leu Ser Thr Met Thr Gly Asp Trp Ile Val Glu Gly Gln Val 2495 2500 2505 Gly Ala Gly Tyr Trp Val Glu Asn Leu Arg Arg Pro Val Leu Phe 2510 2515 2520 Ala Asp Ala Thr Arg Arg Leu Ala Ser Glu Gly Phe Gly Ala Phe 2525 2530 2535 Val Glu Val Ser Ala His Pro Val Leu Val Met Gly Ile Glu Glu 2540 2545 2550 Thr Leu Glu Ala His His Thr Ala Thr Thr Asp Asp Asp Thr Thr 2555 2560 2565 Thr Arg Thr Pro Val Val Thr Val Gly Thr Leu Arg Arg Gly Glu 2570 2575 2580 Gly Gly Trp Asp Gln Phe Leu Arg Ser Leu Ala Gly Leu Phe Val 2585 2590 2595 Arg Gly Ala Val Thr Pro Asp Trp Glu Ser Leu Leu Gly Gly Thr 2600 2605 2610 Arg Pro Arg Val Asp Leu Pro Thr Tyr Ala Phe Gln Arg Arg Arg 2615 2620 2625 Phe Trp Ile Glu Ser Val Arg Lys Glu Ala Val Thr Leu Ala Ala 2630 2635 2640 Asp Pro Val Asp Ala Ala Phe Trp Glu Ala Val Glu Ser Ala Asp 2645 2650 2655 Leu Ala Lys Leu Ala Asp Ser Leu Arg Ile Glu Thr Asp Val Leu 2660 2665 2670 Glu Gly Val Leu Pro Ala Leu Thr Ser Trp Arg Thr Arg Ser Arg 2675 2680 2685 Glu Gln Ser Leu Val Asp Gly Trp Arg Tyr Arg Glu Glu Trp Lys 2690 2695 2700 Pro Val Pro Ala Pro Thr Pro Asn Ser Ala Thr Gly Thr Trp Thr 2705 2710 2715 Val Leu Val Pro Ala Thr His Gln Gly Asp Ala Thr Val Thr Gly 2720 2725 2730 Val Leu Asp Gly Leu Arg Arg Gly Gly Ala Asp Ile Arg Val Leu 2735 2740 2745 Glu Val Thr Ala Thr Asp Arg Glu Ala Leu Ala Glu Gln Leu Arg 2750 2755 2760 Ala Glu Leu Ala Gln Ser Glu Pro Arg Leu Ile Leu Ser Leu Leu 2765 2770 2775 Ala Leu Asp Asp Arg Ala His Pro Arg His Pro Glu Leu Thr Glu 2780 2785 2790 Gly Ile Thr Ala Thr Ile Ala Leu Val Gln Ala Leu Asp Asp Cys 2795 2800 2805 Gly Ala Thr Ala Arg Leu Trp Cys Ala Thr Ser Leu Ala Val Ala 2810 2815 2820 Val Thr Glu Ser Ala Glu Val Leu Asn Pro Val Gln Thr Thr Ala 2825 2830 2835 Trp Gly Met Gly Ala Ser Phe Ala Leu Asp His Pro Glu Thr Trp 2840 2845 2850 Gly Gly Leu Val Asp Leu Pro Ala Asp Ile Asp Thr Arg Thr Ala 2855 2860 2865 Asp Ile Leu Cys Ser Val Leu Ala Ser Asp Leu Gln Glu Asp Gln 2870 2875 2880 Ile Ala Leu Arg Thr Ala Gly Leu Phe Ala Arg Arg Met Val Arg 2885 2890 2895 Ala Arg Leu Asp Glu Ser Ala Val Ala Thr Glu Gln Pro Trp Arg 2900 2905 2910 Pro Asn Gly Thr Val Leu Val Thr Gly Gly Thr Gly Gly Ile Gly 2915 2920 2925 Ser His Val Ala Arg Trp Leu Ala Ala Ala Gly Ala Glu His Leu 2930 2935 2940 Val Leu Thr Ser Arg Arg Gly Ala Glu Ala Pro Gly Ala Ala Glu 2945 2950 2955 Leu Glu Ala Glu Leu Ala Leu Leu Gly Ala Lys Val Thr Leu Ala 2960 2965 2970 Ala Cys Asp Met Gly Asp Arg Glu Ser Val Arg Glu Leu Val Ala 2975 2980 2985 Ala Leu Pro Asp Ala Ala Pro Leu Thr Ala Val Phe His Leu Ala 2990 2995 3000 Gly Ala Leu Pro Asp Gly Glu Arg Arg Leu Ser Ala Thr Thr Phe 3005 3010 3015 Glu Asp Phe Ser Arg Met Thr Arg Ala Lys Ile Gly Gly Ala Val 3020 3025 3030 His Leu Asp Glu Leu Leu Ala Asp Arg Glu Leu Ala Ala Phe Val 3035 3040 3045 Thr Phe Ser Ser Gly Ser Ala Ile Trp Gly Asn Ala Asn Gln Ala 3050 3055 3060 Ala Tyr Gly Ala Ser Asn Ala Phe Leu Asp Gly Leu Val His Asn 3065 3070 3075 Arg Arg Ala Arg Gly Leu Ala Gly Thr Ser Ile Ala Trp Gly Leu 3080 3085 3090 Trp Gly Gly Asp Gly Thr Asp Thr Glu Thr Asp Glu Gln Leu Ser 3095 3100 3105 Arg Ile Gly Val Arg Ser Met Asp Pro Arg Leu Ala Leu Glu Val 3110 3115 3120 Leu Arg Gln Ala Leu Asp Gln Asp Thr Ser His Leu Ile Ala Thr 3125 3130 3135 Asp Ile Asp Trp Gln Arg Phe Ala Pro Val Phe Thr Ile Ala Arg 3140 3145 3150 Pro Arg Pro Leu Leu Asp Gly Ile Ala Glu Val Arg Ala Val Leu 3155 3160 3165 Ser Ala Asp Thr Ala Glu Val Gly Pro Ala Asp Asp Asp Thr Pro 3170 3175 3180 Lys Glu Thr Val Val Thr Arg Leu Ala Gly Leu Ser Pro Ala Glu 3185 3190 3195 Arg Asp His Ala Leu Leu Glu Leu Val Arg Thr Gln Val Ala Ala 3200 3205 3210 Val Leu Arg Tyr Ser Asp Thr Ser Asp Val Glu Gln Asp Gln Ser 3215 3220 3225 Phe Lys Asp Leu Gly Phe Asp Ser Val Thr Ala Val Glu Leu Arg 3230 3235 3240 Asn Lys Leu Thr Arg Gly Val Arg Ala Ala Ala Ala Arg His Gly 3245 3250 3255 Val Phe Asp Tyr Ala Thr Pro Val Ala Leu Ala Ala His Leu Arg 3260 3265 3270 Ser Glu Leu Phe Thr Asp Asp Ala Ala Ala Ser Gly Glu Val Pro 3275 3280 3285 Leu Leu Ala Glu Leu Asp Arg Ile Glu Ala Ala Val Thr Ser Leu 3290 3295 3300 Pro Ser Ala Asp Ile Glu Arg Met His Leu Thr Ser Arg Leu Gln 3305 3310 3315 Ser Leu Val Thr Lys Leu Asn Asp Ile Val Gly Ala Gly Ala Pro 3320 3325 3330 Leu Glu Ala Glu Ala Ile Ala Asp Lys Leu Glu Thr Ala Thr Ala 3335 3340 3345 Asp Asp Ile Phe Ala Phe Ile Asp Lys Asp Leu Gly Leu Asn 3350 3355 3360 7 3808 PRT Streptomyces halstedii sp.HC-34 7 Met Ser Asn Glu Glu Lys Leu Leu Asp Tyr Leu Lys Arg Val Thr Ala 1 5 10 15 Asp Leu His Ala Thr Arg Gln Arg Leu Arg Glu Ala Glu Ser Asp Glu 20 25 30 Gln Glu Pro Ile Ala Val Val Ala Met Gly Cys Arg Tyr Pro Gly Asp 35 40 45 Val Arg Thr Pro Glu Asp Leu Trp Gln Leu Val Ala Thr Gly Gly Asp 50 55 60 Ala Val Thr Glu Phe Pro Ala Asp Arg Gly Trp Asp Phe Asp Thr Leu 65 70 75 80 Leu Gly Gly Asp Ala Gly Ala Ser Gly Ser Thr Tyr Val Ala Arg Gly 85 90 95 Gly Phe Val His Asp Ala Ala Asp Phe Asp Ala Asp Phe Phe Gly Ile 100 105 110 Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Leu Leu 115 120 125 Glu Leu Ala Trp Glu Thr Ser Glu Arg Ala Gly Ile Asp Pro His Ser 130 135 140 Leu Arg Gly Ala Ser Val Gly Val Phe Ala Gly Thr Asn Gly Gln Asp 145 150 155 160 Tyr Ala Asp Leu Met Asp Arg Ala Pro Glu Asp Thr Glu Ala Tyr Leu 165 170 175 Ser Thr Gly Ser Val Ala Ala Val Val Ser Gly Arg Val Ser Tyr Ala 180 185 190 Leu Gly Leu Glu Gly Pro Ser Val Ser Val Asp Thr Ala Cys Ser Ser 195 200 205 Ser Leu Val Ala Leu His Leu Ala Cys Gln Ala Leu Arg Gln Lys Glu 210 215 220 Cys Ser Met Ala Phe Ala Gly Gly Val Thr Ile Met Ser Thr Pro Gly 225 230 235 240 Pro Phe Ile Ala Phe Ser Arg Gln Ser Gly Leu Ala Ser Asp Gly Arg 245 250 255 Cys Lys Ala Phe Ser Asp Asp Thr Asp Gly Thr Gly Trp Gly Glu Gly 260 265 270 Ala Gly Leu Leu Leu Leu Glu Arg Leu Ser Asp Ala Arg Arg Asn Gly 275 280 285 His Gln Val Leu Ala Val Val Arg Gly Ser Ala Leu Asn Gln Asp Gly 290 295 300 Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ser Gln Gln Arg Val 305 310 315 320 Ile Arg Gln Ala Leu Ala Asn Ala Gly Leu Thr Ala Ala Glu Val Asp 325 330 335 Ala Val Glu Ala His Gly Thr Gly Thr Thr Leu Gly Asp Pro Ile Glu 340 345 350 Ala Gln Ala Ile Leu Ala Thr Tyr Gly Gln Ser Arg Glu Gln Asp Gln 355 360 365 Pro Leu Trp Leu Gly Ser Ile Lys Ser Asn Ile Gly His Thr Gln Ala 370 375 380 Ala Ala Gly Val Ser Gly Val Ile Lys Met Val Met Ala Ile Gln Asn 385 390 395 400 Gly Val Leu Pro Lys Thr Leu His Val Ser Glu Pro Ser Ser Val Val 405 410 415 Asp Trp Ser Ala Gly Ala Val Glu Leu Leu Thr Glu Ala Arg Glu Trp 420 425 430 Pro Glu Thr Gly Arg Pro Arg Arg Ala Gly Val Ser Ser Phe Gly Val 435 440 445 Ser Gly Thr Asn Ala His Ile Ile Met Glu Gln Ala Pro Val Pro Glu 450 455 460 Ala Glu Ser Glu Pro Asp Gly Glu Ala Pro Ala Ala Val Ser Gly Leu 465 470 475 480 Pro Val Pro Trp Val Val Ser Gly Lys Thr Ala Asp Ala Leu Arg Ala 485 490 495 Gln Ala Glu Arg Leu Leu Ser Phe Val Ser Ala Asp Ala Asp Val Ser 500 505 510 Val Val Asp Val Ala Tyr Ser Leu Gly Val Ser Arg Ala Gly Leu Glu 515 520 525 His Arg Gly Val Val Val Gly Glu Ser Arg Ala Glu Leu Leu Ala Ala 530 535 540 Leu Glu Ser Leu Ala Ser Gly Val Glu Ser Pro Gly Val Val Thr Gly 545 550 555 560 Arg Val Ala Glu Gly Arg Leu Ala Phe Leu Phe Thr Gly Gln Gly Ala 565 570 575 Gln Arg Val Gly Met Gly Arg Glu Leu Ala Ala Ala Phe Pro Val Phe 580 585 590 Ala Ala Ser Leu Glu Glu Thr Cys Gly Leu Leu Glu Arg Ala Gly Val 595 600 605 Ala Val Arg Glu Val Leu Phe Ala Glu Glu Gly Ser Ala Glu Ala Ala 610 615 620 Leu Leu Thr Arg Thr Val Tyr Ala Gln Ala Ala Leu Phe Ala Val Glu 625 630 635 640 Val Ala Leu Phe Arg Leu Val Glu Ser Phe Gly Val Val Pro Asp Phe 645 650 655 Val Ala Gly His Ser Val Gly Glu Ile Ala Ala Ala His Val Ala Gly 660 665 670 Val Phe Ser Leu Glu Asp Ala Val Ser Leu Val Ala Ala Arg Gly Arg 675 680 685 Leu Met Asp Ala Leu Pro Glu Gly Gly Ala Met Val Ala Val Gln Ala 690 695 700 Thr Glu Glu Asp Val Leu Ala Leu Leu Glu Gly Val Glu Asp Ala Ser 705 710 715 720 Ile Ala Ala Ile Asn Gly Pro Asp Ala Val Val Val Ser Gly Thr Glu 725 730 735 Ala Gly Val Ala Arg Val Val Asp Val Leu Arg Glu Arg Gly Ala Lys 740 745 750 Thr Lys Arg Leu Asp Val Ser His Ala Phe His Ser Pro Leu Met Glu 755 760 765 Pro Met Leu Ala Glu Phe Ala Thr Val Val Glu Gly Leu Ser Phe Ala 770 775 780 Ala Pro Thr Ile Pro Val Val Ser Asn Val Ser Gly Ala Val Ala Asp 785 790 795 800 Ala Glu Leu Ser Ser Pro Gly Tyr Trp Val Arg His Val Arg Glu Ala 805 810 815 Val Arg Phe Gly Ala Gly Val Glu Thr Leu Leu Gly Ala Gly Val Ser 820 825 830 Ser Phe Leu Glu Ile Gly Pro Asp Gly Val Leu Ser Gly Met Ala Arg 835 840 845 Gly Ser Ile Ser Asp Gly Ala Asp Val Gly Cys Val Pro Val Met Arg 850 855 860 Arg Gly Arg Gly Glu Val Arg Glu Phe Leu Thr Gly Leu Ser Arg Ile 865 870 875 880 Ala Val Arg Gly Val Pro Val Ser Trp Gly Pro Leu Leu Ala Gly Gly 885 890 895 Arg Arg Val Glu Leu Pro Thr Tyr Ala Phe Gln Arg Arg Arg Phe Trp 900 905 910 Leu Glu Ala Gly His Ser Val Thr Asp Ala Ser Gly Leu Gly Gln Thr 915 920 925 Ala Ala Gly His Pro Leu Ile Gly Ala Val Val Ser Leu Ala Gly Gly 930 935 940 Asp Gly Ala Val Leu Thr Gly Arg Val Ser Leu Asn Thr His Pro Trp 945 950 955 960 Leu Gly Asp His Arg Val Ala Ser Ser Val Val Phe Pro Gly Thr Gly 965 970 975 Phe Val Glu Leu Leu Met Arg Ala Gly Asp Glu Val Gly Cys Gly Arg 980 985 990 Leu Glu Glu Leu Asn Gln Glu Ala Pro Leu Val Val Pro Asp Arg Gly 995 1000 1005 Ala Val Gln Ile Gln Val Thr Val Glu Ala Pro Asn Ala Val Gly 1010 1015 1020 Glu Arg Pro Val Ala Val Tyr Ser Arg Leu Glu Asp Thr Asp Thr 1025 1030 1035 Asp Ala Pro Trp Thr Arg His Ala Ser Gly Leu Leu Ser Pro Thr 1040 1045 1050 Thr Ala Ser Ala Asp Phe Asp Phe Thr Ala Trp Pro Pro Ala Gly 1055 1060 1065 Ala Asp Pro Leu Ser Val Asp Gly Met Tyr Asp Arg Pro Asp Ser 1070 1075 1080 Gly Leu Val Tyr Gly Pro Leu Phe Gln Gly Leu Thr Ala Ala Trp 1085 1090 1095 Arg Lys Gly Asp Glu Val Tyr Ala Glu Ile Glu Leu Pro Glu Gly 1100 1105 1110 Ala Ala Val Asp Ala Ala Arg Phe Gly Met His Pro Ala Leu Leu 1115 1120 1125 Asp Ala Ala Leu His Ala Leu Gly Phe Ser Ala Ser Tyr Glu Asp 1130 1135 1140 Gln Glu Glu Asp Gly Thr Val Ala Arg Leu Pro Phe Ser Trp Ser 1145 1150 1155 Gly Val Ser Leu Phe Ala Ser Gly Ala Ser Val Leu Arg Val Cys 1160 1165 1170 Val Arg His Val Ala Arg Asp Arg Val Ser Leu Leu Val Ala Asp 1175 1180 1185 Gly Val Gly Val Pro Val Ala Val Val Glu Ser Leu Val Leu Arg 1190 1195 1200 Ala Ile Ser Ala Gly Ala Val Ala Val Ala Gly Val Gly Ser Gly 1205 1210 1215 Val Gly Gly Gly Leu Phe Glu Val Val Trp Ser Pro Val Val Gly 1220 1225 1230 Val Arg Gly Val Asp Val Ser Gly Val Val Val Leu Glu Ala Gly 1235 1240 1245 Val Gly Val Gly Gly Asp Gly Val Ser Val Val Gly Gly Val Leu 1250 1255 1260 Glu Gly Leu Gln Gly Val Leu Gly Gly Gly Ser Gly Ser Arg Val 1265 1270 1275 Val Val Val Thr Arg Gly Ala Val Gly Ser Gly Gly Val Val Asp 1280 1285 1290 Val Ser Gly Ala Gly Val Trp Gly Leu Val Arg Ser Val Gln Ala 1295 1300 1305 Glu His Pro Gly Arg Leu Val Leu Val Asp Val Gly Val Glu Gly 1310 1315 1320 Asp Val Gly Val Gly Val Gly Leu Ala Leu Gly Ser Gly Glu Glu 1325 1330 1335 Gln Val Val Val Arg Gly Gly Glu Val Phe Val Pro Arg Leu Ala 1340 1345 1350 Arg Val Ser Val Val Ala Ala Asp Val Val Pro Asp Ala Gly Val 1355 1360 1365 Asp Gly Ala Asp Ile Arg Gly Gly Leu Gly Asp Gly Val Val Leu 1370 1375 1380 Val Thr Gly Gly Thr Gly Gly Leu Gly Ala Leu Val Ala Arg His 1385 1390 1395 Val Val Val Glu Arg Gly Val Arg Arg Leu Val Leu Val Ser Arg 1400 1405 1410 Arg Gly Leu Gly Ala Pro Gly Ala Val Gly Leu Val Ala Glu Leu 1415 1420 1425 Glu Ser Leu Gly Ala Val Val Glu Val Val Ala Cys Asp Val Ser 1430 1435 1440 Asp Arg Val Ala Leu Ala Gly Val Val Gly Gly Ile Gly Ser Asp 1445 1450 1455 Leu Ser Ala Val Val His Thr Ala Gly Val Val Asp Asp Gly Val 1460 1465 1470 Val Glu Ser Met Ser Val Gly Arg Val Ala Ser Val Phe Gly Pro 1475 1480 1485 Lys Ala Asp Ala Ala Trp Phe Leu His Glu Leu Thr Arg Asp Met 1490 1495 1500 Gly Leu Ser Ala Phe Val Leu Phe Ser Ser Met Ala Gly Thr Val 1505 1510 1515 Gly Gly Gly Gly Gln Ser Asn Tyr Ala Ala Ala Asn Ala Tyr Leu 1520 1525 1530 Asp Gly Leu Ala Glu Tyr Arg Arg Gly Leu Gly Leu Ala Ala Thr 1535 1540 1545 Ser Leu Ala Trp Gly Leu Trp Glu Asp Thr Ala Asn Gly Gly Met 1550 1555 1560 Thr Gly His Leu Ala Glu Ala Asp Arg Thr Arg Met Ala Arg Gly 1565 1570 1575 Gly Val Phe Pro Leu Ala Leu Asp Glu Gly Leu Ala Leu Phe Asp 1580 1585 1590 Ala Ala Leu Ala Thr Gly Lys Ala Thr Leu Val Pro Val His Leu 1595 1600 1605 Asp Thr Thr Ala Leu Arg Ala His Ala Asp Glu Leu Pro Ala Leu 1610 1615 1620 Phe Arg Asp Leu Val Arg Ala Pro Lys Arg Arg Thr Ala Ala Glu 1625 1630 1635 Gly Arg Ala Ala Asp Ser Ala Asp Asp Leu Ala Gly Arg Leu Ala 1640 1645 1650 Gly Leu Ala Ala Glu Ala Arg Arg Pro Leu Val Leu Gly Val Val 1655 1660 1665 Arg Ala Gln Val Ala Gln Val Leu Gly Tyr Ala Ser Ala Asp Leu 1670 1675 1680 Val Glu Pro Glu Arg Ala Phe Gln Asp Leu Gly Phe Asp Ser Leu 1685 1690 1695 Thr Ala Val Glu Leu Arg Asn Gly Leu Thr Ala Val Ala Gly Val 1700 1705 1710 Arg Leu Pro Ala Thr Leu Val Phe Asp Tyr Pro Ser Thr Asp Ile 1715 1720 1725 Leu Thr Asp Phe Leu Leu Ala Glu Leu Ser Gly Lys Val Ala Val 1730 1735 1740 Ala Ala Pro Leu Ala Pro Leu Ala Thr Thr Gly Pro Val His Asp 1745 1750 1755 Asp Pro Ile Val Val Ile Gly Met Gly Cys Arg Tyr Pro Gly Gly 1760 1765 1770 Val Arg Ser Pro Glu Asp Leu Trp Arg Leu Val Ala Asp Gly Arg 1775 1780 1785 Asp Ala Ile Ser Glu Phe Pro Thr Asp Arg Gly Trp Asp Leu Asp 1790 1795 1800 Ala Leu Tyr His Pro Asp Pro Asp His Ala Gly Thr Ser Tyr Thr 1805 1810 1815 Arg Glu Gly Gly Phe Leu His Asp Ala Ala Asp Phe Asp Ala Asp 1820 1825 1830 Phe Phe Gly Ile Ser Pro Arg Glu Ala Ile Val Met Asp Pro Gln 1835 1840 1845 Gln Arg Leu Leu Leu Glu Thr Ser Trp Glu Ala Phe Glu Gln Ala 1850 1855 1860 Gly Ile Val Pro Ala Asp Leu Lys Gly Thr Gln Thr Gly Val Phe 1865 1870 1875 Ala Gly Val Met Tyr His Asp Tyr Gly Thr Arg Ile Val Asp Ile 1880 1885 1890 Pro Glu Gly Ala Glu Gly Tyr Leu Gly Thr Gly Ile Ser Gly Ser 1895 1900 1905 Val Val Ser Gly Arg Val Ala Tyr Thr Leu Gly Leu Glu Gly Pro 1910 1915 1920 Ala Val Thr Ile Asp Thr Ala Cys Ser Ser Ser Leu Val Ala Leu 1925 1930 1935 His Ser Ala Ala His Ala Leu Arg Gln Gly Glu Cys Ser Met Ala 1940 1945 1950 Ile Ala Gly Gly Val Thr Val Met Ala Gly Pro Asp Thr Phe Ile 1955 1960 1965 Asp Phe Ser Arg Gln Arg Gly Leu Ala Thr Asn Gly Arg Cys Lys 1970 1975 1980 Ala Phe Ser Ala Asp Ala Asp Gly Thr Gly Trp Gly Glu Gly Val 1985 1990 1995 Gly Val Leu Val Leu Glu Arg Leu Ser Asp Ala Arg Lys Asn Gly 2000 2005 2010 His Glu Val Leu Ala Val Ile Arg Gly Ser Ala Leu Asn Gln Asp 2015 2020 2025 Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ser Gln Gln 2030 2035 2040 Arg Val Ile Arg Gln Ala Leu Ala Ser Ala Gly Leu Thr Thr Ser 2045 2050 2055 Asp Val Asp Ala Val Glu Ala His Gly Thr Gly Thr Thr Leu Gly 2060 2065 2070 Asp Pro Ile Glu Ala Gln Ala Val Leu Ala Thr Tyr Gly Gln Asp 2075 2080 2085 Arg Ala Ala Asp Gln Pro Leu Trp Leu Gly Ser Ala Lys Ser Asn 2090 2095 2100 Phe Gly His Thr Gln Ala Ala Ala Gly Val Ala Gly Val Ile Lys 2105 2110 2115 Met Val Met Ala Ile Arg Asn Gly Val Leu Pro Lys Thr Leu His 2120 2125 2130 Val Ser Glu Pro Ser Thr His Val Asp Trp Ser Ala Gly Ala Val 2135 2140 2145 Glu Leu Leu Ala Glu Ala Arg Glu Trp Pro Glu Thr Gly Arg Pro 2150 2155 2160 Arg Arg Ala Gly Val Ser Ser Phe Gly Val Ser Gly Thr Asn Ala 2165 2170 2175 His Val Ile Val Glu Gln Ala Pro Thr Glu Glu Gln Ala Pro Ala 2180 2185 2190 Asp Ala Pro Ala Pro Thr Asp Ala Pro Ala Gly Thr Pro Val Pro 2195 2200 2205 Trp Ile Val Ser Gly Arg Thr Ala Asp Ser Leu Arg Asp Gln Ala 2210 2215 2220 Arg Arg Leu Leu Glu His Leu Asp Arg Asn Gly Asp Leu Asp Pro 2225 2230 2235 Gln Asp Val Ala Arg Ala Leu Leu Thr Thr Arg Thr Arg Phe His 2240 2245 2250 His Arg Ala Ala Val Val Ala Thr Glu Arg Gln Asp Ile Val Ala 2255 2260 2265 Ala Leu Glu Ala Leu Ala Asp Gly Arg Pro Val Ser Gly Leu Val 2270 2275 2280 Gln Gly Thr Ala Thr Thr Met Ala Lys Ser Ala Phe Leu Phe Thr 2285 2290 2295 Gly Gln Gly Ala Gln Arg Val Gly Met Gly Arg Glu Leu Ala Ala 2300 2305 2310 Glu Phe Pro Val Phe Ala Ala Ser Leu Glu Gln Thr Cys Gly Leu 2315 2320 2325 Leu Glu Arg Ala Gly Val Ala Val Arg Glu Val Leu Phe Ala Glu 2330 2335 2340 Glu Gly Ser Ala Glu Ala Ala Leu Leu Thr Arg Thr Val Tyr Ala 2345 2350 2355 Gln Ala Ala Leu Phe Ala Val Glu Val Ala Leu Phe Arg Leu Val 2360 2365 2370 Glu Ser Phe Gly Val Val Pro Asp Phe Val Ala Gly His Ser Val 2375 2380 2385 Gly Glu Ile Ala Ala Ala His Val Ala Gly Val Phe Ser Leu Glu 2390 2395 2400 Asp Ala Val Ser Leu Val Ala Ala Arg Gly Arg Leu Met Asp Ala 2405 2410 2415 Leu Pro Glu Gly Gly Ala Met Val Ala Val Gln Ala Thr Glu Glu 2420 2425 2430 Asp Val Leu Ala Leu Leu Glu Gly Val Glu Asp Ala Ser Ile Ala 2435 2440 2445 Ala Ile Asn Gly Pro Asp Ala Val Val Val Ser Gly Thr Glu Thr 2450 2455 2460 Gly Val Ala Arg Val Val Asp Val Leu Arg Glu Arg Gly Ala Lys 2465 2470 2475 Thr Lys Arg Leu Asp Val Ser His Ala Phe His Ser Pro Leu Met 2480 2485 2490 Glu Pro Met Leu Ala Asp Phe Ala Arg Val Val Ala Gly Leu Ser 2495 2500 2505 Tyr Glu Asp Pro Ala Ile Pro Val Val Ser Asn Val Ser Gly Ser 2510 2515 2520 Met Ala Asp Gly Glu Leu Ser Thr Pro Gly Tyr Trp Val Arg His 2525 2530 2535 Val Arg Glu Ala Val Arg Phe Gly Ala Gly Val Glu Thr Leu Leu 2540 2545 2550 Gly Ala Gly Val Ser Ser Phe Leu Glu Ile Gly Pro Asp Gly Val 2555 2560 2565 Leu Ser Gly Met Ala Arg Thr Ser Val Pro Glu Gly Ala Asp Val 2570 2575 2580 Glu Cys Ala Pro Leu Met Arg Arg Asp Arg Ala Glu Val Arg Glu 2585 2590 2595 Phe Leu Thr Gly Leu Ser Arg Leu Ala Val Arg Gly Val Pro Val 2600 2605 2610 Ser Trp Ser Pro Leu Val Ala Gly Gly Arg Arg Val Glu Leu Pro 2615 2620 2625 Thr Tyr Ala Phe Gln Arg Arg Arg Phe Trp Leu Asp Ala Gly His 2630 2635 2640 Ser Val Thr Asp Ala Ser Gly Leu Gly Gln Thr Ala Ala Gly His 2645 2650 2655 Pro Leu Ile Gly Ala Val Val Gly Leu Ala Gly Gly Asp Gly Val 2660 2665 2670 Val Leu Thr Gly Arg Val Ser Leu His Thr His Pro Trp Leu Ala 2675 2680 2685 Asp His Gln Val Ala Gly Val Thr Leu Leu Pro Gly Thr Gly Phe 2690 2695 2700 Val Glu Leu Ala Val Arg Ala Gly Asp Glu Val Gly Cys Gly Arg 2705 2710 2715 Leu Glu Glu Leu Thr Leu Glu Ala Pro Leu Val Val Pro Asp Arg 2720 2725 2730 Gly Ala Val Gln Leu Gln Val Val Val Gly Gly Leu Glu Glu Ser 2735 2740 2745 Gly Val Arg Thr Val Ser Val Tyr Ser Arg Ala Glu Asp Thr Asp 2750 2755 2760 Asn Pro Asp Thr Pro Trp Thr Arg His Ala Ser Gly Ala Leu Gly 2765 2770 2775 Thr Ala Ala Asp Pro Ala Asp Phe Asp Leu Thr Ala Trp Pro Pro 2780 2785 2790 Ala Gly Thr Glu Ala Val Glu Ile Gly Asp Phe Tyr Gly Glu Leu 2795 2800 2805 Ala Ala Thr Pro Asp Gly Leu Val Tyr Gly Pro Leu Phe Gln Gly 2810 2815 2820 Leu Thr Ala Ala Trp Arg Lys Gly Asp Glu Val Tyr Ala Glu Ile 2825 2830 2835 Glu Leu Pro Glu Gly Ala Ala Val Asp Ala Ala Arg Phe Gly Met 2840 2845 2850 His Pro Ala Leu Leu Asp Ala Ala Leu His Ala Val Gly Leu Ser 2855 2860 2865 Asn Asp Ala Asp Ala Asp Ala Asp Ala Gly Thr Ala Gln Glu Asp 2870 2875 2880 Gly Thr Val Ala Arg Leu Pro Phe Ala Trp Ser Gly Val Thr Leu 2885 2890 2895 His Arg Ser Gly Ala Thr Arg Leu Arg Leu Ser Val Arg Pro Thr 2900 2905 2910 Gly Gly Asp Ser Tyr His Leu Arg Ile Ala Asp Ala Val Gly Ala 2915 2920 2925 Pro Val Ala Thr Val Gly Glu Leu Leu Leu Arg Gly Ile Ser Ala 2930 2935 2940 Glu Gln Leu Ala Arg Ala Gly Thr Asp Arg Pro Asp Ala Leu Phe 2945 2950 2955 Arg Leu Glu Trp Glu Ala Leu Arg Gly Asp Gly Ala Thr Thr Ala 2960 2965 2970 Gly Glu Trp Ala Leu Leu Gly Gly Asp Pro Tyr Gly Leu Ala Pro 2975 2980 2985 Ala Arg Ala Val Pro Tyr Gly Asp Leu Asp Ala Leu Ala Ala Glu 2990 2995 3000 Ala Glu Gly Gly Thr Pro Pro Glu Val Val Leu Leu Pro Leu Thr 3005 3010 3015 Val Pro Ala Gly Glu Glu Pro Asp Ala Gly Glu Arg Ala Ala His 3020 3025 3030 Arg Ala Leu Arg Ala Val Arg Ser Trp Leu Ala Asp Asp Arg Phe 3035 3040 3045 Ala Ala Ala Thr Leu Val Leu Met Thr Arg Gly Ala Leu Ala Ala 3050 3055 3060 Thr Pro Gly Asp Glu Val Thr Asp Val Ala Gly Ala Glu Val Trp 3065 3070 3075 Gly Leu Val Arg Ser Ala Gln Thr Glu His Pro Gly Arg Phe Val 3080 3085 3090 Leu Val Asp Ser Asp Gly Ser Glu Ala Ser Ala Arg Ala Leu Pro 3095 3100 3105 Ala Ala Val Ala Ser Gly Glu Pro Gln Leu Ala Leu Arg Ala Gly 3110 3115 3120 Thr Val Asn Ala Ala Arg Leu Gly Arg Val Glu Arg Ala Gly Ala 3125 3130 3135 Glu Ala Val Ala Thr Phe Asp Pro Glu Arg Thr Val Leu Ile Thr 3140 3145 3150 Gly Gly Thr Gly Ala Leu Ala Gly Gln Leu Ala Arg His Leu Ala 3155 3160 3165 Arg Ala Tyr Gly Val Arg His Leu Leu Leu Ala Gly Arg Arg Gly 3170 3175 3180 Pro Ser Ala Pro His Ala Ala Glu Leu Val Ala Glu Leu Ala Glu 3185 3190 3195 Leu Gly Ala Leu Ala Glu Val Val Ala Cys Asp Val Ala Asp Arg 3200 3205 3210 Glu Ala Leu Thr Ala Leu Leu Ala Ala Val Pro Ala Asp Arg Pro 3215 3220 3225 Leu Gly Ala Val Val His Thr Ala Gly Val Leu Asp Asp Gly Leu 3230 3235 3240 Val Glu Ser Leu Thr Pro Glu Arg Leu Asp Ala Val Leu His Pro 3245 3250 3255 Lys Ala Thr Ala Ala Leu Leu Leu Asp Glu Leu Thr Arg Asp Ala 3260 3265 3270 Asp Leu Thr Ala Phe Val Leu Phe Ser Ser Ala Ala Gly Thr Leu 3275 3280 3285 Gly Ser Pro Gly Gln Ala Asn Tyr Ala Ala Ala Asn Ala Gly Leu 3290 3295 3300 Asp Ala Leu Ala Val Arg Arg Arg Gly Gln Gly Leu Pro Gly Leu 3305 3310 3315 Ser Leu Gly Trp Gly Leu Trp Gln Ala Asp Gly Gly Met Gly Gly 3320 3325 3330 Ala Leu Ser Gly Gly Asp Gln Ala Arg Ile Ala Arg Gly Gly Val 3335 3340 3345 Ala Ala Leu Thr Thr Asp His Gly Leu Ala Leu Phe Asp Thr Ala 3350 3355 3360 Cys Ala Gly Pro Asp Ala Val Val Leu Pro Met Leu Leu Asp Leu 3365 3370 3375 Arg Pro Gln Asp Asp Val Pro His Leu Leu Arg Ser Leu Val Ser 3380 3385 3390 Ala Arg Arg Lys Gly Ala Ser Ala Gly Ala Arg His Glu Gly Pro 3395 3400 3405 Ala Glu Leu Arg Arg Arg Leu Ala Ala Ala Thr Pro Asp Glu Arg 3410 3415 3420 Tyr Glu His Leu Leu Gly Leu Val Arg Ser Cys Thr Ala Val Val 3425 3430 3435 Leu Gly His Arg Gly Pro Gln Asp Val Asp Pro Gly Val Gly Phe 3440 3445 3450 Leu Glu Ser Gly Phe Asp Ser Leu Thr Ala Met Glu Leu Arg Asn 3455 3460 3465 Gln Leu Asn Glu Ala Thr Gly Leu Arg Leu Ala Ala Thr Val Val 3470 3475 3480 Phe Asp His Thr Thr Pro Ala Asp Leu Ala Arg His Leu Val Asp 3485 3490 3495 Gly Val Ala Asp Thr Val Ala Ala Ala Pro Gly Gln Gln Pro Ala 3500 3505 3510 Pro Arg Ser Asp Asp Asp Ala Asp Thr Leu Ser Gly Leu Phe Arg 3515 3520 3525 Thr Ala Val Arg Ala Gly Gln Val Thr Lys Gly Val Asp Leu Leu 3530 3535 3540 Arg Ala Val Ala Glu Leu Arg Pro Ala Phe His Ser Ala Asp Glu 3545 3550 3555 Leu Gly Asp Asp Leu Pro Val Pro Val Arg Leu Ala Gln Gly Pro 3560 3565 3570 Ser Ala Ala Arg Leu Phe Cys Phe Ala Ser Pro Met Ala Met Gly 3575 3580 3585 Gly Thr His Gln Tyr Ala Arg Leu Ala Ala His Phe Arg Gly Val 3590 3595 3600 Arg Glu Val Ser Ala Leu Pro Met Pro Gly Phe Ala Thr Gly Asp 3605 3610 3615 Leu Leu Pro Ala Thr Ala Glu Ala Val Val Glu Val Phe Gly Arg 3620 3625 3630 Ser Leu Leu Arg Ala Ala Gly Asp Glu Pro Phe Val Leu Leu Gly 3635 3640 3645 Tyr Ser Ala Gly Gly Val Phe Ala His Ala Val Ala Ala Trp Leu 3650 3655 3660 Glu Ser Glu Gly Cys Ala Pro Ala Ala Val Val Leu Leu Asp Ser 3665 3670 3675 Tyr Arg Ala Asp Gly Gly Thr Ser Met Asp Gly Asp Phe Trp Val 3680 3685 3690 Ser Met Val Glu Gly Leu Phe Ser Arg Glu Glu Val Phe Gly Arg 3695 3700 3705 Phe Thr Ser Ala Arg Leu Ser Ala Met Gly Arg Tyr Ala Arg Leu 3710 3715 3720 Val Gly Glu Val Lys Thr Gly Glu Val Lys Ala Pro Val Leu Phe 3725 3730 3735 Val Arg Pro Glu Arg Ser Leu Ser Ala Ser Ala Asp Ala Gly Gly 3740 3745 3750 Val Gly Gly Gly Asp Ala Gly Ala Ala Ala Ala Thr Asp Asp Trp 3755 3760 3765 Arg Ala Ser Trp Asp Thr Ala Glu Thr Val Leu Glu Val Ala Gly 3770 3775 3780 Asp His Phe Asp Ile Ile Glu Ser Gln Ala Ala Ala Thr Ala Asp 3785 3790 3795 Ala Val Glu Gly Trp Leu Ala Asp Arg Val 3800 3805 8 236 PRT Streptomyces halstedii sp.HC-34 8 Met Tyr Glu Glu Asp Phe Ala Arg Val Tyr Asp Asp Ile Tyr Arg Arg 1 5 10 15 His Lys Asp Tyr Ala Gly Glu Ala Ala Arg Ile Arg Glu Leu Ala Leu 20 25 30 Glu Arg Asn Pro Gly Ala Ala Asp Leu Leu Asp Val Gly Cys Gly Thr 35 40 45 Gly Glu His Leu Ala Leu Leu Arg Asp Asp Phe Ala Val Thr Gly Val 50 55 60 Asp Leu Ser Ala Pro Met Val Arg Val Ala Glu Ala Lys Leu Pro Gly 65 70 75 80 Val Pro Val His Glu Gly Asp Met Arg Thr Phe Gly Leu Asp Arg Ser 85 90 95 Phe Asp Val Ile Cys Ser Met Tyr Ser Ser Val Gly Tyr Leu Glu Thr 100 105 110 Leu Asp Gly Leu Phe Ala Ala Leu Lys Asn Met Ala His His Leu Arg 115 120 125 Pro Gly Gly Val Leu Ile Ile Glu Pro Trp Ile Leu Arg Asp Ser Trp 130 135 140 Asn Gly Gly Asp Leu Val Glu Ala Ser Phe Glu Asn Glu Gly Gly Lys 145 150 155 160 Val Val Arg Met Gly Arg Trp Thr Thr Arg Ala Gly Arg Ser His Val 165 170 175 Glu Met His Tyr Leu Val Thr Ser Gly Asp Asp Pro Val Arg His Phe 180 185 190 Val Asp Glu Gln Glu Leu Ser Leu Phe Ser Lys Asp Glu Tyr Glu Glu 195 200 205 Ala Phe Arg Ala Ala Gly Cys Ser Val Glu Tyr Leu Pro Asp Gly Tyr 210 215 220 Val Asp Arg Gly Val Phe Val Gly Val Arg Gln Pro 225 230 235 9 397 PRT Streptomyces halstedii sp.HC-34 9 Leu Arg Leu Gly Ala Gly Glu Arg Asn Asp Glu Gln Val Thr Asp Ser 1 5 10 15 Pro Val Phe Arg Glu Pro Leu His Val Gly Arg Pro Asn Ile Gly Ser 20 25 30 Arg Ala Arg Leu Thr Glu Arg Leu Glu Gly Ala Leu Asp Arg Leu Tyr 35 40 45 Leu Thr Asn Gly Pro Leu Val Arg Glu Phe Glu Glu Arg Leu Ala Glu 50 55 60 Val Ala Gly Val Asp His Cys Val Ala Val Cys Asn Ala Thr Ile Gly 65 70 75 80 Leu Gln Val Ala Ala Lys Ala Ala Gly Ile Arg Gly Gly Asp Glu Val 85 90 95 Ile Val Pro Ala Phe Thr Trp Val Ala Thr Ala Ala Ala Leu Asp Trp 100 105 110 Ile Gly Ile Val Pro Val Phe Cys Asp Ala Asp Glu Thr Thr Gly Asn 115 120 125 Ile Asp Trp Thr Lys Val Glu Ala Leu Ile Gly Pro Arg Thr Arg Gly 130 135 140 Ile Met Gly Val His Val Phe Gly Arg Pro Cys Glu Val Asp Glu Leu 145 150 155 160 Glu Glu Ile Ala Gly Arg His Gly Leu Pro Leu Leu Phe Asp Ser Ala 165 170 175 His Ala Ile Gly Cys Thr Tyr Lys Gly Arg Pro Val Gly Gly Phe Gly 180 185 190 Thr Ala Glu Val Tyr Ser Phe His Ala Thr Lys Phe Val Asn Ser Phe 195 200 205 Glu Gly Gly Ala Ile Val Thr Arg Asp Ala Glu Phe Ala Glu Arg Cys 210 215 220 Arg Glu Leu Arg Asn Phe Gly Ile Thr Ser Ala Gly Glu Ile Arg Ser 225 230 235 240 Gly Gly Thr Asn Ala Lys Met Asn Glu Ala Ala Ala Ala Met Gly Leu 245 250 255 Thr Ser Leu Glu Val Met Asp Ser Leu Met Glu Ala Asn Arg Ile Asn 260 265 270 His Gly Arg Tyr Glu Lys Gly Leu Asp Gly Leu Pro Gly Val Trp Val 275 280 285 Arg Gly Gln Ala Glu Gly Glu Arg Ala Asn His Gln Tyr Leu Val Ile 290 295 300 Glu Ile Asp Ala Ala Val Ala Gly Ile His Arg Asp Glu Val His Thr 305 310 315 320 Ala Leu Ile Ala Gln Asn Val Leu Ser Arg Arg Tyr Phe His Pro Ser 325 330 335 Cys His Gln Val Glu Pro Tyr Leu Ser Asp Pro Ala Arg His Ala Pro 340 345 350 His Pro Leu Pro His Ala Glu Ala Leu Ala Glu Arg Val Leu Ala Leu 355 360 365 Pro Thr Gly Thr Thr Val Gly Pro Ser Glu Ile Asp Gln Val Cys Asp 370 375 380 Ile Ile Arg Arg Cys Val Ser Ala Arg Thr Pro Ala Arg 385 390 395 10 493 PRT Streptomyces halstedii sp.HC-34 10 Met Glu Ile Ser Met Thr Glu Thr Leu Ser Thr Leu Pro Pro Thr His 1 5 10 15 Thr Gly Asp Glu Ser Leu Ala Val Arg Ile Ala Lys Ser Val Ser Val 20 25 30 Val Asp Asp Gly Ala Leu His Ser Leu Asp Glu Phe His Asp Trp Phe 35 40 45 Thr Ala Arg Gly Gln Arg Thr Ala His Val Glu Arg Val Pro Leu Asp 50 55 60 Glu Leu Thr Gly Trp Ser Ser Asp Pro Val Thr Gly Asn Ile Gly His 65 70 75 80 Asp Ser Gly Lys Phe Phe Ser Val Gln Gly Leu Ser Val Glu Leu Pro 85 90 95 Gly Ala Pro Val Pro Ala Trp Ala Gln Pro Ile Ile Asn Gln Pro Glu 100 105 110 Ile Gly Ile Leu Gly Ile Leu Ile Lys Glu Phe Asn Gly Val Leu His 115 120 125 Cys Leu Met Gln Ala Lys Leu Glu Pro Gly Asn Arg Asn Gly Leu Gln 130 135 140 Leu Ser Pro Thr Val Gln Ala Thr Arg Ser Asn Tyr Thr Arg Val His 145 150 155 160 Gln Gly Asn Pro Val Pro Tyr Val Gly Tyr Phe Gln Asp Thr Ser Ala 165 170 175 Asn Arg Val Ile Thr Asp Ala Leu Gln Ser Glu Gln Gly Ser Trp Phe 180 185 190 Tyr Gln Lys Arg Asn Arg Asn Met Val Val Glu Thr Glu Ala Glu Ile 195 200 205 Glu Gln His Glu Ala Phe Met Trp Leu Thr Ile Gly Gln Leu His Arg 210 215 220 Leu Leu Ala Ile Asp Asp Leu Ile Asn Met Asp Thr Arg Thr Val Leu 225 230 235 240 Ser Cys Leu Pro Phe Ser Gly Ala Gln Leu Ala Glu Gln Leu Pro Gly 245 250 255 Thr Gly Gly Asp Leu Arg Met Pro Ile Leu Arg Ser Cys Ser Glu Asp 260 265 270 Gln Gly Ser Leu His Thr Thr Gly Asp Leu Leu Ser Trp Ile Thr Asp 275 280 285 Ala Arg Thr Arg Asn Glu Val Arg Thr Arg Leu Thr Pro Leu Arg Asp 290 295 300 Val Ala Gly Trp Arg Arg Thr Pro Asp Ala Ile Thr His Asp Thr Gly 305 310 315 320 Arg Phe Phe Asp Val Met Ala Val Arg Ile Glu Thr Asp Gly Asp Arg 325 330 335 Glu Val Arg Gln Trp Thr Gln Pro Met Ile Ala Pro Ala Gly Ile Gly 340 345 350 Ile Val Ala Phe Leu Val Lys Arg Ile Asp Gly Val Leu His Val Leu 355 360 365 Ala His Ala Arg Val Glu Pro Gly Tyr Leu Asp Val Val Glu Leu Ser 370 375 380 Pro Thr Val Met Cys Thr Pro Gly Asn Tyr Glu Gly Leu Pro Ala Ala 385 390 395 400 Ala Arg Pro Pro Phe Leu Gly Glu Val Leu Ser Ala Arg Pro Glu Gln 405 410 415 Val Arg Phe Glu Thr Ile Leu Ser Glu Glu Gly Gly Arg Phe Tyr His 420 425 430 Ala Gln Asn Arg Tyr Ile Ile Val Glu Ser Asp Ile Asp Val Ala Pro 435 440 445 Glu Leu Ala Ser Glu Tyr Arg Trp Met Ala Leu His Gln Met Val Gly 450 455 460 Leu Leu Arg His Ser His Tyr Val Asn Val Gln Ala Arg Ser Leu Ile 465 470 475 480 Ala Cys Leu His Ser Leu Ser Gly Ala Gln Gly Arg Asn 485 490 11 330 PRT Streptomyces halstedii sp.HC-34 11 Val Thr Met Leu Tyr Arg Gln Leu Gly Arg Thr Ala Leu Lys Val Ser 1 5 10 15 Pro Leu Cys Leu Gly Thr Leu Asn Leu Gly Val Arg Thr Thr Arg Asp 20 25 30 Glu Ala Phe Ala Leu Met Asp Glu Ala Leu Glu Gln Gly Ile Asn Phe 35 40 45 Phe Asp Thr Ala Asn Gln Tyr Gly Trp Gln Val His Lys Gly Leu Thr 50 55 60 Glu Glu Ile Ile Gly Glu Trp Phe Ala Gln Gly Gly Gly Arg Arg Glu 65 70 75 80 Arg Val Val Leu Gly Thr Lys Val Cys Asn Pro Met Ser Asp Leu Pro 85 90 95 Asn Asp Gln Gly Leu Ser Ala Arg His Ile Ile Ala Ser Cys Glu Asp 100 105 110 Ser Leu Arg Arg Leu Arg Thr Asp Trp Ile Asp Val Tyr Gln Leu His 115 120 125 Asn Ile Asp Pro Thr Ala Ser Trp Asp Glu Val Trp Gln Ala Met Glu 130 135 140 Thr Leu Val His Gln Gly Lys Ile Arg Tyr Val Gly Ser Ser Asn Phe 145 150 155 160 Ala Gly Trp His Leu Ala Asp Ala Gln Ala Ala Ala Ala Arg Arg Asn 165 170 175 Phe Leu Gly Leu Val Ser Glu Gln Cys Cys Tyr Asn Leu Ala Thr Arg 180 185 190 Tyr Val Glu Met Glu Val Val Pro Ala Ala Arg Ala His Gly Ile Gly 195 200 205 Val Leu Ala Trp Ser Pro Leu His Gly Gly Leu Leu Ser Gly Ala Leu 210 215 220 Arg Lys Leu Asp Glu Gly Thr Ala Val Lys Thr Ala Gln Gly Arg Ala 225 230 235 240 Gln Ile Ala Leu Arg Thr Met Arg Asp Thr Val Glu Gln Tyr Glu Lys 245 250 255 Leu Cys Glu Ser Ile Ser Ala Asp Pro Ser Gln Val Ala Leu Ala Trp 260 265 270 Leu Leu Ser Arg Pro Gly Leu Thr Ala Ala Val Ile Gly Pro Arg Thr 275 280 285 Thr Gly His Leu Ala Ser Ala Leu Glu Thr Leu Asp Met Thr Leu Pro 290 295 300 Glu Asp Ile Leu Ala Pro Leu Asp Glu Leu Phe Pro Pro Ile Gly Asn 305 310 315 320 Gly Gln Pro Ala Pro Ala Thr Trp Leu Ala 325 330 12 158 PRT Streptomyces halstedii sp.HC-34 12 Met Pro Asp Ile Thr Ser Glu Arg Leu Pro Asp Gln Asp His His Leu 1 5 10 15 Pro Ala Glu Arg Ala Arg Pro Val Leu Ile Ser Ser Val Ala Ser Asp 20 25 30 Ser His Thr Trp Asn Leu Val Phe Leu Gln Leu Leu Ile Glu Glu Leu 35 40 45 Gly His Glu Val Ile Asn Leu Gly Pro Cys Val Pro Asp Glu Leu Leu 50 55 60 Ile Ala Glu Cys Arg Asp Arg Arg Pro Gly Leu Val Val Ile Ser Thr 65 70 75 80 Val Asn Gly His Gly Tyr Gln Asp Gly Leu Arg Val Ile Gly Lys Leu 85 90 95 Arg Ala Cys Glu Asp Leu Ala Asn Ile Pro Val Val Ile Gly Gly Lys 100 105 110 Leu Gly Val Ser Gly Pro Gly Gln Ser Tyr Ala Ala Glu Leu Ala Gly 115 120 125 Ala Gly Phe Asp Ala Val Phe Pro Asp Gly Ala Glu Ala Val Ser Ser 130 135 140 Phe Thr Arg Tyr Val Glu Lys Leu Pro Gln Arg Val Val Ser 145 150 155 13 469 PRT Streptomyces halstedii sp.HC-34 13 Leu Thr Gly Phe Gly Ala Tyr Val Arg Ser Val His Arg Arg Gly Glu 1 5 10 15 Leu Val Val Gln Pro Arg Met Gly Phe Ser Gly Thr Val Glu Met Arg 20 25 30 Ala Gly Leu Ala Ala Thr Arg Ala Ala Asp Ala Ala Thr Val Gly Thr 35 40 45 Ile Thr Leu Asp Ser Tyr Thr Arg Val Gly Glu Leu Ala Ala Ala Glu 50 55 60 Glu Ala Leu Arg Ser Gly Ile Ala Leu Asn Gly Tyr Pro Ile Val Thr 65 70 75 80 Tyr Asp Glu Ser Thr Thr Arg Glu Leu Leu Ala Gly Ile Ala Gly Glu 85 90 95 Asp Phe Pro Val Gln Ile Arg His Gly Ser Ala Thr Pro Leu His Ile 100 105 110 Phe Gly Ala Leu Thr Arg Ala Gly Leu Asp Ala Thr Glu Gly Gly Pro 115 120 125 Val Ser Tyr Cys Leu Pro Tyr Gly Arg Ile Pro Leu Glu Gln Ser Val 130 135 140 Thr Asn Trp Thr Arg Cys Cys Glu Glu Phe Ala Arg Leu Arg Gly Leu 145 150 155 160 Gly Arg Glu Pro His Leu Glu Thr Phe Gly Gly Cys Met Leu Gly Gln 165 170 175 Leu Cys Pro Pro Ser Gln Leu Val Ala Ile Ser Met Leu Glu Ala Leu 180 185 190 Phe Phe His Gln His Gly Ile Arg Ser Ile Ser Leu Ser Tyr Ala Gln 195 200 205 Gln Thr His Gln Gly Gln Asp Glu Glu Ala Val Leu Ala Leu Arg Arg 210 215 220 Leu His Arg Glu Leu Leu Pro Asp Ala Asp Cys His Ile Val Ile Tyr 225 230 235 240 Ala Tyr Met Gly Val Tyr Pro Thr Thr Pro Glu Gly Ala His Ala Leu 245 250 255 Leu Gly Arg Ala Ala Glu Leu Ala Val Ala Thr Gly Ala Glu Arg Leu 260 265 270 Ile Val Lys Thr Ala Ala Glu Ala His Arg Ile Pro Thr Ile Gly Glu 275 280 285 Asn Val Ala Ala Leu Glu His Ala Ala Thr Val Ser Arg Ala Ala Arg 290 295 300 Arg Ala Thr Ala Leu Pro Ala Gly His Ser Ala Ala Pro Ala Ala Thr 305 310 315 320 Asp Pro Thr Ala Ala Leu Thr Ala Arg Pro Gly Thr Tyr Ala Asp Gly 325 330 335 Ser Ala Ala Leu Thr Ala Gly Pro Gly Ala Ala Arg Asp Gly Ser Thr 340 345 350 Asp Ser Ala Val Tyr Ala Glu Ala Arg Ala Leu Ile Glu Ala Val Met 355 360 365 Asn Cys Gly Pro Asp Val Gly Thr Ala Leu Phe Arg Ala Phe Lys Arg 370 375 380 Gly Tyr Leu Asp Ile Pro Tyr Cys Leu His Pro Asp Asn Met Gly Arg 385 390 395 400 Ser Arg Ser Tyr Ile Asp Asp Thr Gly Arg Leu Gln Trp Ala Glu Thr 405 410 415 Gly Met Leu Pro Leu Gly Asn Ala Arg Lys Ser Gly Thr Gly Arg Ser 420 425 430 Val Ser Ser Thr Asp Leu Ile Ser Ala Leu Ser Phe Val Gln Arg Thr 435 440 445 Tyr Asp Gln Leu Ala Phe Pro Glu Ser Arg Glu Pro Leu Arg Ile Pro 450 455 460 Arg Gln Gln Arg Pro 465 14 299 PRT Streptomyces halstedii sp.HC-34 14 Met Ser Lys Pro Pro Ser Ala Lys Gly Thr Val Pro Phe Gly Gln Tyr 1 5 10 15 Arg Thr Trp Tyr Arg Val Thr Gly Asp Leu His Ser Gly Lys Pro Pro 20 25 30 Val Val Leu Leu His Gly Gly Pro Gly Ser Thr His Asp Tyr Leu Leu 35 40 45 Ala Met Thr Ser Leu Thr Glu Ala Gly Trp Pro Val Val His Tyr Asp 50 55 60 Gln Leu Gly Asn Gly Gly Ser Thr His Leu Pro Glu Lys Gly Glu Asp 65 70 75 80 Phe Trp Thr Val Gln Leu Phe Glu Asp Glu Leu Asp Asn Leu Leu Asn 85 90 95 Gln Leu Gly Ile Ala Gly Asp Tyr Val Leu Phe Gly Gln Ser Trp Gly 100 105 110 Gly Met Leu Gly Ser Val His Ala Ala Arg Arg Pro Ala Gly Leu Arg 115 120 125 Gly Leu Val Val Ala Asn Ala Pro Ala Ser Met Lys Ile Trp Leu Gln 130 135 140 Glu Met Ala Arg Leu Arg Ala Leu Leu Pro Pro Asp Val Gln Glu Thr 145 150 155 160 Leu Leu Lys His Glu Ala Ala Arg Thr Thr Asp Thr Glu Glu Tyr Phe 165 170 175 His Ala Met Arg Ala Phe Tyr Asp Arg His Val Cys Arg Ile Val Pro 180 185 190 Trp Pro Arg Asp Phe Ala Ala Thr Phe Met Glu Ile Tyr Asn Asp Pro 195 200 205 Thr Val Tyr Thr Thr Met Asn Gly Pro Asn Glu Phe His Val Ile Gly 210 215 220 Thr Leu Arg Asp Trp Ser Val Glu Asp Cys Leu Pro Asp Ile Gln Val 225 230 235 240 Pro Thr Met Val Leu Ile Gly Arg His Asp Glu Ala Thr Pro Ala Thr 245 250 255 Val Lys Pro Phe Leu Asp Leu Val Pro Asp Val Arg Tyr Glu Val Leu 260 265 270 Glu Asn Ser Ser His Val Pro His Leu Glu Glu Pro Glu Arg Phe His 275 280 285 Glu Val Met Ile Asp Tyr Leu Glu Ser Leu Val 290 295 15 327 PRT Streptomyces halstedii sp.HC-34 15 Val Asn Ala Thr Val Glu Thr Thr Gln His Asp Val Glu Gly Thr Gly 1 5 10 15 Ala Ala Gly Ala Thr Ala Met Leu Phe Pro Gly Met Gly Pro Ala Ala 20 25 30 Phe Ser Asp Val Gly Arg Phe Met Val Thr Asn Arg Tyr Thr Arg Glu 35 40 45 Leu Leu Ala Glu Ala Asp Asp Thr Leu Gly Tyr Ser Leu Val Asp Arg 50 55 60 Phe Arg Gln Ala Glu Gly Asp Tyr Ser Glu Tyr Ala Gln Ile Ala Phe 65 70 75 80 Leu Val Asn Cys Val Ala Leu Ala Arg Trp Ala Glu Gln Thr Met Asp 85 90 95 Leu Thr Pro Arg Ile Cys Ala Gly Ala Ser Phe Gly Glu Lys Ser Val 100 105 110 Ala Ala Tyr Ser Gly Ala Leu Thr Phe Ala Asp Ala Val Arg Met Thr 115 120 125 Ala Gly Leu Ala Arg Cys Met Asp Glu Tyr Phe Arg Thr Glu His Leu 130 135 140 Gly Val Val Thr His Ser Phe Val Arg Ala Pro Arg Glu Arg Leu Asp 145 150 155 160 Glu Ile Leu Ala Glu Leu Asp Glu Arg Gly Glu Trp His Glu Ile Ser 165 170 175 Cys His Ile Asp His Asp Phe Phe Met Leu Thr Leu His Glu Arg Asn 180 185 190 Ser Val Trp Leu Glu Gly Arg Leu Arg Ser Val Gly Ala Met Pro Leu 195 200 205 Tyr Ala Met Arg Pro Pro Met His Ala Ala Ala Phe Gly Gly Leu Arg 210 215 220 Asp Lys Ala Glu Glu Glu Val Ile Ala Pro Leu Thr Phe His Asp Pro 225 230 235 240 Thr Leu Pro Val Val Ala Asp Gln Asp Gly Lys Val Leu Thr Thr Gly 245 250 255 Asp Glu Val Arg Thr Met Leu Leu Glu Ser Phe Val Arg Pro Leu Arg 260 265 270 Trp Pro Asp Val Ile Ser Ser Leu Gln Asp Gln Gly Val Thr Arg Val 275 280 285 Cys Val Ala Gly Pro Asp Ser Leu Phe Gly Arg Val Gly Thr Thr Thr 290 295 300 Arg Ala Phe Glu Val Ile Ala Ala Thr Pro Arg Leu Ala Leu Gln Pro 305 310 315 320 Arg Ala Arg Thr Thr Ser Arg 325 16 82 PRT Streptomyces halstedii sp.HC-34 16 Met Trp Asp Ala Gln Phe Glu Asn Leu Leu Arg Arg Tyr Leu Pro Phe 1 5 10 15 Leu Ser Ala Asp Gln Pro Leu Glu Gln Asp Ile Asn Leu Arg Asp Ile 20 25 30 Gly Leu Asp Ser Leu Gly Thr Val Glu Leu Leu Ser Glu Leu Glu Asn 35 40 45 Thr Tyr Asp Val His Phe Gln Asp Glu Ala Leu Thr Lys Glu Thr Phe 50 55 60 Glu Thr Pro Gly Val Leu Trp Lys Thr Leu Ser Gln Met Val Glu Pro 65 70 75 80 Arg His 17 524 PRT Streptomyces halstedii sp.HC-34 17 Met His Ala Ala Asp His Ala Leu His Ala Arg Phe Leu Arg Gly Leu 1 5 10 15 Ala Cys Ala Pro Asp Arg Pro Ala Val Arg Phe Gly Gly Arg Thr Leu 20 25 30 Thr Tyr Ala Gln Ala His Arg Thr Ala Leu Thr Trp Ala Gly Ser Leu 35 40 45 Leu Arg Ala Thr Pro Glu Pro Pro Ala Ala Val Gly Val Leu Ala Asp 50 55 60 Lys Gly Ile Pro Ala Tyr Leu Gly Ile Leu Thr Ala Leu Tyr Ala Gly 65 70 75 80 Ala Ala Val Val Pro Leu Arg Pro Asp Phe Pro Ala Ala Arg Thr Ala 85 90 95 Glu Met Met Arg Ala Ala Gly Val Thr Ala Val Ile Ala Asp Gly Arg 100 105 110 Gly Arg Arg Leu Leu Pro Glu Leu Leu Ala Asp Arg Arg Asp Thr Ala 115 120 125 Val Leu Ala Ala Asp Glu Glu Gly Ala Pro Ala Asp Glu Ser Pro Ala 130 135 140 Asp Gly Ser Ala Pro Gly Arg Arg Val Ala Ile Asp Glu Gly Tyr Ala 145 150 155 160 Leu Thr Ala Pro Arg Asp Val Val Pro Asp Asp Thr Ala Tyr Val Leu 165 170 175 Phe Thr Ser Gly Ser Thr Gly Arg Pro Lys Gly Val Pro Leu Ser His 180 185 190 Gly Asn Ile Ala His Tyr Phe Glu Val Leu Asp Ala Arg Tyr Asp Phe 195 200 205 Thr Ala Asp Asp Val Phe Thr Gln Thr Phe Asp Leu Asn Phe Asp Cys 210 215 220 Ser Leu Phe Asp Leu Phe Cys Ala Trp Gly Ala Gly Ala Ser Val Ile 225 230 235 240 Gln Ile Pro Pro Gln Ala Tyr Arg Asp Leu Pro Ser His Leu Ala Glu 245 250 255 Gln Gly Val Thr Val Trp Phe Ser Thr Pro Ser Ser Ile Ala Leu Val 260 265 270 Arg Arg Leu Gly Gly Leu Ala Pro Gly Ser Leu Pro Thr Leu Arg Trp 275 280 285 Ser Phe Phe Ala Gly Glu Ala Leu Lys Cys Ala Asp Thr Glu Asp Trp 290 295 300 Gln Arg Ala Ala Pro Ala Ser Phe Val Glu Asn Leu Tyr Gly Pro Thr 305 310 315 320 Glu Leu Thr Val Thr Val Thr Ala His Arg Trp Ser Pro Glu Val Ser 325 330 335 Pro Val Val Gly Ala Asn Gly Val Val Pro Ile Gly Pro Leu His Lys 340 345 350 Gly Leu Asp His Val Leu Ile Asp Ala Gly Gly Leu Pro His Pro Asp 355 360 365 Thr Gly Glu Leu Cys Val Thr Gly Pro Gln Met Ala Gly Arg Tyr Leu 370 375 380 Asp Pro Ala Asp Asp His Gly Arg Phe Leu Asp His Asp Gly Arg Arg 385 390 395 400 Trp Tyr Arg Thr Gly Asp Arg Val Arg Leu Ala Pro Gly Gly Glu Leu 405 410 415 Val Tyr Leu Gly Arg Met Asp Ala Gln Val Gln Ile Gln Gly Trp Arg 420 425 430 Val Glu Leu Ala Glu Val Asp His Ala Leu Gln Gly Cys Glu Gly Val 435 440 445 Gly Glu Ala Val Thr Val Gly Ala Ala Thr Asp Ala Gly Thr Glu Leu 450 455 460 Val Val Phe Tyr Thr Ala Pro Ala Pro Val Pro Pro Val Arg Phe Ala 465 470 475 480 Ala Val Leu Arg Ala Thr Leu Pro Asp Gly Val Val Pro Arg His Tyr 485 490 495 Arg His Val Ala Glu Leu Pro Leu Asn Ser Asn Arg Lys Ile Asp Arg 500 505 510 Arg Ala Leu Thr Ala Arg Ala Glu Glu Leu Leu Gly 515 520 18 478 PRT Streptomyces halstedii sp.HC-34 18 Met Glu Asp Ala Phe Gly Thr Trp Thr Tyr Gln Glu Leu Leu Asn His 1 5 10 15 Ser Gln Ala Phe Ser Ala Trp Leu Asp Gly Lys Gly Val Ala Arg Gly 20 25 30 Glu Arg Ile Val Val Gln Leu Pro Asn Ile Arg Gln Thr Val Ala Val 35 40 45 Phe Tyr Gly Ala Cys Arg Arg Gly Val Val Phe Val Pro Leu Asn Pro 50 55 60 Gly Met Lys Pro Phe His Leu Arg Ser Val Ile Ala Asp Ala Asp Pro 65 70 75 80 Arg Leu Val Ile Ala Glu Asp Glu Thr Ala Ala Asp Arg Leu Arg Asp 85 90 95 Val Thr Asp Leu Pro Val Tyr Ser Ile Asp Ser Leu Trp Ala Asp Val 100 105 110 Glu Arg Leu Arg Asp Ala Gly Ala Gly Ala Glu Ala Val Glu Val Ser 115 120 125 Pro Glu Asp Leu Ala Val Leu Ile Tyr Thr Ser Gly Ser Thr Ala Ala 130 135 140 Pro Lys Ala Val Ala Cys Pro His Gln Gln Ile Val Phe Ala Ala Ser 145 150 155 160 Ser Ile Asn Ala Val Leu Gly Tyr His Ala Glu Asp Ile Val Phe Cys 165 170 175 Arg Met Ser Val Ser Trp Asp Phe Gly Leu Tyr Lys Val Leu Ile Ser 180 185 190 Thr Leu Thr Gly Ala Lys Leu Val Leu Ala Gly Gly Glu Pro Asp Ile 195 200 205 Ala Leu Val Lys Ser Leu Arg Glu Ser Gly Ala Thr Met Met Pro Ile 210 215 220 Val Pro Ser Leu Ala Ser Met Leu Thr Thr Leu Ile Arg Arg Asp Pro 225 230 235 240 Glu Gly Ala Pro Thr Leu Arg Met Phe Thr Asn Ser Ala Ala Ala Leu 245 250 255 Pro Gln Val Thr Ile Asp Ala Leu Arg Ser Ala Phe Pro Gly Ala Gln 260 265 270 Val Val Arg Met Tyr Gly Gln Thr Glu Cys Lys Arg Ile Ser Ile Met 275 280 285 Pro Pro His Leu Glu His Glu Arg Pro Asp Ser Val Gly Leu Pro Leu 290 295 300 Pro Gly Thr Thr Ile Glu Ile Leu Asp Glu Asp Gly Thr Leu Leu Pro 305 310 315 320 Pro Gly Glu Pro Gly Glu Ile Thr Val Thr Gly Pro His Val Met Ala 325 330 335 Gly Tyr Trp Arg Ala Pro Glu Ile Thr Ala Arg Ala Tyr Arg Arg Asp 340 345 350 Glu Thr Thr Gly Ala Met Arg Leu His Thr Gly Asp Tyr Gly His Leu 355 360 365 Asp Glu Asp Gly Phe Leu Tyr Phe Gly Gly Arg Arg Asp Asp Met Phe 370 375 380 Lys Arg Lys Gly Thr Arg Met Ser Thr Val Glu Ile Glu Ala Ala Ala 385 390 395 400 Leu Asp Ile Pro Gly Val Thr Ala Ala Val Ala Leu Pro Pro Thr Ala 405 410 415 Thr Arg Asp Leu Ala Leu Cys Val Ala Ser Asp Leu Glu Pro His Asp 420 425 430 Val Leu Arg Ser Leu Ala Glu Arg Leu Glu Pro Ala Lys Val Pro Ala 435 440 445 Thr Cys Arg Ile Val Asn Asp Phe Pro Leu Thr Leu Asn Gly Lys Ser 450 455 460 Glu Arg Lys Gln Leu Ala Arg Leu Leu Asp Gly Ser Asp Lys 465 470 475 19 414 PRT Streptomyces halstedii sp.HC-34 19 Val Asn Gln Tyr Glu Glu Leu Ala Asp Gln Tyr Gly Thr Pro Leu Tyr 1 5 10 15 Val Tyr Asp Leu Asp Arg Val Ala Glu Ala Arg His Asp Leu Arg Thr 20 25 30 Ser Leu Pro Asp Glu Val Glu Ile Tyr Tyr Ala Leu Lys Ala Asn Pro 35 40 45 His Pro Gln Val Ala Gly Ala Leu Arg Ser Gly Glu Gly Arg Glu Cys 50 55 60 Arg Ala Glu Ile Ser Ser Val Gly Glu Leu Ala Ala Ala Leu Thr Ala 65 70 75 80 Gly Phe Arg Ala Ser Glu Ile Leu Tyr Thr Gly Pro Gly Lys Thr Asp 85 90 95 Gly Glu Leu Asp Glu Ala Ile Gly Lys Gly Val Lys Thr Phe Cys Val 100 105 110 Glu Ser Leu Thr Asp Leu Gln His Val Gly Ala Val Ala Leu Arg His 115 120 125 Gly Val Val Ala Asp Cys Leu Leu Arg Ile Asn Ser Ala Thr Ala Ser 130 135 140 Ala Thr Thr Ser Ile Arg Met Thr Gly Thr Pro Ser Gln Phe Gly Ile 145 150 155 160 Asp Ser Glu Thr Leu Val Asp Ala Met Pro Glu Leu Arg Ala Val Pro 165 170 175 Gly Thr Arg Ile Thr Gly Leu His Phe Phe Pro Leu Ser Asn Ala Arg 180 185 190 Asp Glu Ala Ser Leu Ile Gly Glu Phe Arg His Thr Ile Ala Tyr Ala 195 200 205 Ala Gly Leu Ala Glu Glu Thr Gly Leu Thr Leu Glu Phe Leu Asp Ile 210 215 220 Gly Gly Gly Phe Ala His Pro Tyr Gly Ala Pro Gly Glu Arg Pro Val 225 230 235 240 Tyr Arg Glu Leu Arg Thr Glu Leu Ala Ala Ala Leu Asp Glu His Phe 245 250 255 Pro His Trp Arg Glu Gly Ala Pro Arg Ile Ala Val Glu Thr Gly Arg 260 265 270 Tyr Gln Thr Ser Gly Ala Gly Thr Leu Leu Thr Arg Val Val Asn Ile 275 280 285 Lys Val Ser Arg Gly Arg Lys Phe Val Val Ile Asp Ala Gly Ile Asn 290 295 300 Thr Phe Gly Gly Met Ser Gly Leu Gly Arg Leu Leu Pro Val Ala Val 305 310 315 320 Glu Pro Glu Tyr Thr Gly Ser Ala Glu Ala Thr Glu Leu Thr Asp Val 325 330 335 Ala Ser Leu Ala Gly Pro Leu Cys Thr Pro Gly Asp Ile Leu Gly Arg 340 345 350 Glu Ile Arg Leu Pro Glu Leu Ala Pro Gly Asp Leu Val Thr Ile Pro 355 360 365 Asn Ala Gly Ala Tyr Gly Val Thr Ala Ser Leu Leu Met Phe Leu Gly 370 375 380 Arg Pro Ala Pro Val Glu Val Val Leu Lys Gly Gly Lys Val Val Ser 385 390 395 400 Ala Ser Arg Leu Glu His His Arg Thr Pro Ala Thr Pro Gly 405 410 20 5836 PRT Streptomyces halstedii sp.HC-34 20 Met Ser Pro Ala Leu Ala Arg Ser Lys Arg Met Ser Glu Ser Glu Asn 1 5 10 15 Pro Val Ser Ala Thr Thr Ala Gly Ala Asp Glu Thr Pro Asp Thr Arg 20 25 30 Thr Ala Leu Ala Arg Arg Leu Ala Gly Leu Ser Pro Ala Glu Gln Glu 35 40 45 Gln His Leu Val Asp Met Val His Arg His Thr Val Ala Ala Leu Gln 50 55 60 Ala Val Ala Pro Leu Thr Pro Asp Gln Val Asp Val Gln Arg Pro Phe 65 70 75 80 Leu Glu Leu Gly Phe Asp Ser Leu Ala Ala Val Asp Leu His Lys Arg 85 90 95 Leu Thr Gly Glu Thr Gly Leu Glu Leu Pro Val Thr Val Ala Phe Asp 100 105 110 Phe Pro Thr Pro Val Leu Val Ala Glu Glu Ile Arg Arg Ile Ala Phe 115 120 125 Gly Ile Arg Pro Ala Pro Leu Ala Pro Val Val Ala Thr Gly Asn Leu 130 135 140 Asp Asp Asp Pro Ile Ala Ile Ile Gly Ile Gly Cys Arg Phe Pro Gly 145 150 155 160 Gly Ile Asn Ser Ala Glu Glu Leu Trp Gln Leu Val Met Asp Glu Ala 165 170 175 Glu Val Leu Ser Gly Phe Pro Thr Asn Arg Gly Trp Asp Val Glu Gly 180 185 190 Ile Tyr Asp Pro Asp Pro Gly Lys Pro Gly Lys Ser Tyr Val Arg Glu 195 200 205 Gly Gly Phe Leu Gln Asp Ala Gly Asp Phe Asp Ala Asp Phe Phe Gly 210 215 220 Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Val 225 230 235 240 Leu Glu Thr Ala Trp Glu Ala Phe Glu Arg Ala Gly Ile Asp Pro Gly 245 250 255 Ser Leu His Gly Ser Lys Ala Gly Val Phe Ile Gly Ala Glu Val His 260 265 270 Glu Tyr Gly Thr Arg Val His Glu Ala Pro Glu Gly Leu Asp Gly Tyr 275 280 285 Leu Met Thr Gly Asn Ala Pro Ser Val Ala Ser Gly Arg Ile Ala Tyr 290 295 300 Ser Leu Gly Leu Glu Gly Pro Ala Val Thr Ile Asp Thr Ala Cys Ser 305 310 315 320 Gly Ser Leu Val Ala Leu His Leu Ala Ala His Ser Leu Arg Gln Gly 325 330 335 Glu Ser Ser Leu Ala Ile Ala Gly Gly Val Thr Val Met Gly Asn Pro 340 345 350 Gly Met Phe Ala Ala Phe Ser Arg Gln Arg Gly Leu Ala Ala Asp Gly 355 360 365 Arg Cys Lys Pro Phe Ala Ala Ala Ala Asp Gly Thr Gly Phe Ser Glu 370 375 380 Gly Val Gly Val Phe Val Val Glu Arg Leu Ala Asp Ala Arg Arg Asn 385 390 395 400 Gly His Pro Val Leu Gly Ile Val Lys Gly Ser Ala Ile Asn Gln Asp 405 410 415 Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ser Gln Gln Arg 420 425 430 Leu Ile Leu Gln Ala Leu Ala Asn Ala Gly Leu Lys Pro Ala Asp Val 435 440 445 Asp Thr Met Glu Ala His Gly Thr Gly Thr Lys Leu Gly Asp Pro Ile 450 455 460 Glu Ala Gln Ala Ile Leu Ala Thr Tyr Gly Gln Glu Arg Glu Glu Gly 465 470 475 480 Arg Pro Leu Trp Leu Gly Ser Ile Lys Ser Asn Leu Gly His Thr Gln 485 490 495 Ala Ala Gly Gly Ala Ala Ser Leu Ile Lys Met Leu Met Gly Met Arg 500 505 510 His Gly Lys Leu Pro Arg Ser Leu His Ile Asp Ala Pro Thr Pro His 515 520 525 Val Asp Trp Thr Thr Gly Asp Val Ala Leu Leu Thr Glu Thr Arg Asp 530 535 540 Trp Asp Ala Pro Asp Arg Pro Arg Arg Ala Gly Val Ser Ala Phe Gly 545 550 555 560 Ile Ser Gly Thr Asn Ala His Val Ile Ile Glu Glu Ala Pro Glu Phe 565 570 575 Glu Pro Ser Ala Val Glu Pro Val Ala Gly Ser Gly Val Thr Pro Pro 580 585 590 Trp Val Leu Ser Ala Arg Ser Ala Asp Ala Leu Arg Gly Gln Ala Glu 595 600 605 Arg Leu Leu Ser Phe Val Ser Thr Asp Ala Asp Val Ser Val Val Asp 610 615 620 Val Ala Tyr Ser Leu Gly Val Ser Arg Ala Gly Leu Glu His Arg Gly 625 630 635 640 Val Val Leu Gly Glu Ser Arg Glu Glu Leu Ile Ala Ala Leu Glu Ser 645 650 655 Leu Ala Ser Gly Ala Glu Ala Pro Gly Val Val Thr Gly Arg Val Ala 660 665 670 Glu Gly Arg Leu Ala Phe Leu Phe Thr Gly Gln Gly Ala Gln Arg Val 675 680 685 Gly Met Gly Arg Glu Leu Ala Ala Glu Phe Pro Val Phe Ala Ala Ser 690 695 700 Leu Glu Glu Thr Cys Asp Leu Leu Asp Val Gly Leu Glu Asp Gln Asp 705 710 715 720 His Ser Leu Arg Glu Val Leu Phe Ala Glu Glu Gly Ser Ala Glu Ala 725 730 735 Ala Leu Leu Thr Arg Thr Val Tyr Ala Gln Ala Ala Leu Phe Ala Val 740 745 750 Glu Val Ala Leu Phe Arg Leu Val Glu Ser Phe Gly Val Val Pro Asp 755 760 765 Phe Val Ala Gly His Ser Val Gly Glu Ile Ala Ala Ala His Val Ala 770 775 780 Gly Val Phe Ser Leu Glu Asp Ala Thr Met Leu Val Ala Ala Arg Gly 785 790 795 800 Arg Leu Met Asp Ala Leu Pro Glu Gly Gly Thr Met Val Ala Val Gln 805 810 815 Ala Thr Glu Glu Asp Val Leu Ala Leu Leu Glu Gly Val Glu Asp Ala 820 825 830 Ser Ile Ala Ala Ile Asn Gly Pro Asp Ala Val Val Val Ser Gly Thr 835 840 845 Glu Thr Gly Val Ala Arg Val Val Asp Val Leu Arg Asp Arg Gly Ala 850 855 860 Lys Thr Lys Arg Leu Asp Val Ser His Ala Phe His Ser Pro Leu Met 865 870 875 880 Glu Pro Met Leu Thr Glu Phe Arg Arg Val Ala Glu Val Leu Glu Tyr 885 890 895 Gln Ala Pro Arg Ile Ala Val Val Ser Asn Val Ser Gly Ser Val Ala 900 905 910 Gly Thr Glu Leu Ala Thr Pro Glu Tyr Trp Val Thr His Val Arg Glu 915 920 925 Ala Val Arg Phe Ser Ala Gly Val Arg Thr Leu Leu Gly Ala Gly Val 930 935 940 Ser Ser Phe Leu Glu Ile Gly Pro Asp Gly Val Leu Ser Gly Met Ala 945 950 955 960 Arg Gly Ser Val Ser Asp Gly Ala Asp Val Gly Cys Val Pro Val Met 965 970 975 Arg Arg Gly Arg Gly Glu Val Arg Glu Phe Leu Thr Gly Leu Ser Arg 980 985 990 Ile Ala Val Arg Gly Val Pro Val Thr Trp Glu Pro Leu Ile Glu Gly 995 1000 1005 Ala Arg Arg Val Glu Leu Pro Thr Tyr Ala Phe Gln Arg Arg Trp 1010 1015 1020 Phe Trp Leu Glu Ala Gly Arg Ser Thr Thr Asp Ala Leu Gly Leu 1025 1030 1035 Gly Gln Thr Ala Ala Glu His Pro Leu Val Gly Ala Val Val Gly 1040 1045 1050 Leu Ala Gly Gly Asp Gly Val Val Leu Thr Gly Arg Val Ser Leu 1055 1060 1065 His Thr His Pro Trp Leu Ala Asp His Gln Val Ala Gly Val Thr 1070 1075 1080 Leu Leu Pro Gly Thr Gly Phe Val Glu Leu Ala Val Arg Ala Gly 1085 1090 1095 Asp Glu Val Gly Cys Gly Arg Leu Glu Glu Leu Thr Leu Glu Ala 1100 1105 1110 Pro Leu Val Val Pro Asp Arg Gly Ala Val Gln Leu Gln Val Val 1115 1120 1125 Val Gly Ala Leu Glu Glu Ser Asp Val Arg Thr Val Ser Val Tyr 1130 1135 1140 Ser Arg Ala Glu Glu Asp Asp Val Trp Thr Arg His Ala Thr Gly 1145 1150 1155 Phe Val Gly Ala Ala Val Asp Gly Gly Leu Asn Leu Glu Ala Trp 1160 1165 1170 Pro Pro Pro Gly Ala Arg Ala Val Asp Val Ser Asp Val Tyr Ala 1175 1180 1185 Gly Leu Ala Asp Gln Gly Tyr Gly Tyr Gly Pro Val Phe Gln Gly 1190 1195 1200 Leu Arg Ser Val Trp Arg Gly Asp Gly Glu Val Phe Ala Glu Val 1205 1210 1215 Val Leu Pro Glu Gly Ala Gln Ala Asp Ala Ser Ala Phe Gly Leu 1220 1225 1230 His Pro Ala Leu Leu Asp Ala Ala Leu His Ala Thr Asp Tyr Leu 1235 1240 1245 Asp Pro Glu Ser Ala Val Glu Gly Thr His Leu Pro Phe Ala Trp 1250 1255 1260 Thr Gly Val Ser Leu His Ala Thr Gly Ala Ser Glu Leu Arg Val 1265 1270 1275 Arg Ile Thr Ala Thr Gly Asn Asp Gly Tyr Ala Leu Asp Leu Ala 1280 1285 1290 Asp Thr Thr Gly Arg Pro Val Ala Thr Val Gln Ser Leu Val Leu 1295 1300 1305 Arg Pro Val Thr Glu Glu Gln Leu Arg Ser Ala Gln Gly Gly Asn 1310 1315 1320 Gly Pro Asp Ser Leu Phe Arg Val Glu Trp Ala Pro Val Thr Ala 1325 1330 1335 Asp Leu Thr Ala Ser Gly Ala Gly Trp Ala Val Leu Gly Ala Gly 1340 1345 1350 Ala Pro Glu Leu Ala Ala Ala Leu Thr Ala Ala Gly Thr Pro Gly 1355 1360 1365 Thr Ala Tyr His Gly Thr Ala Glu Leu Ser Ala Ala Val Asp Gly 1370 1375 1380 Gly Thr Thr Pro Asp Val Val Ala Val Gln Leu Pro Ser Ala Gly 1385 1390 1395 Ala Ala Asp Ala Asp Leu Pro Asp Ala Val Arg Ala Thr Leu Asn 1400 1405 1410 Thr Ala Leu Glu Phe Val Gln Asn Trp Leu Ala Asp Glu Arg Leu 1415 1420 1425 Ala Glu Thr Arg Leu Val Val Val Thr Arg Asp Ala Val Thr Val 1430 1435 1440 Asp Thr Ala Ala Gly Gly Pro Asp Leu Thr Val Ala Pro Val Trp 1445 1450 1455 Gly Leu Ile Arg Ser Ala Gln Ala Glu Asn Pro Gly Arg Ile Leu 1460 1465 1470 Leu Ala Asp Ile Asp Gly Thr Asp Gln Ser Arg Thr Ala Leu Ala 1475 1480 1485 Ala Ile Thr Ala Ala Asp Glu Pro Glu Leu Ala Phe Arg Asn Gly 1490 1495 1500 Asn Ala Tyr Ala Pro Arg Leu Val Arg Ser Val Ser Glu Gly Gly 1505 1510 1515 Leu Val Pro Pro Ser Asp Ala Ala Ser Trp Arg Leu Asp Val Leu 1520 1525 1530 Ser Gln Gly Thr Leu Glu Asn Leu Ala Leu Ile Pro Ser Asp Ala 1535 1540 1545 Asp Glu Arg Thr Leu Ala Pro Gly Glu Val Arg Ile Ala Val Arg 1550 1555 1560 Ala Ala Gly Val Asn Phe Arg Asp Val Leu Val Ala Leu Gly Met 1565 1570 1575 Tyr Pro Thr Lys Ala Asp Ile Gly Gly Glu Ala Ala Gly Leu Val 1580 1585 1590 Leu Glu Val Gly Pro Gly Val Thr Asp Phe Thr Pro Gly Asp Arg 1595 1600 1605 Val Met Gly Leu Phe Asp Thr Ala Phe Gly Pro His Ala Ile Thr 1610 1615 1620 Asp His Arg Thr Leu Val Pro Met Pro Thr Gly Trp Thr Tyr Ala 1625 1630 1635 Gln Ala Ala Thr Ala Pro Leu Val Phe Ala Thr Ala Tyr Tyr Gly 1640 1645 1650 Leu Val Asp Leu Ala Glu Leu Arg Ser Gly Glu Ser Ala Leu Ile 1655 1660 1665 His Ala Ala Ala Gly Gly Val Gly Met Ala Ala Val Gln Ile Ala 1670 1675 1680 Arg His Leu Gly Ala Glu Val Tyr Gly Thr Ala Ser Pro Gly Lys 1685 1690 1695 Trp Asn Ala Leu Arg Ala Ala Gly Leu Asp Asp Asn His Ile Ala 1700 1705 1710 Ser Ser Arg Asp Thr Thr Phe Glu Gln Lys Phe Leu Ala Asn Ser 1715 1720 1725 Gly Gly Arg Gly Val Asp Val Val Leu Asp Ala Leu Thr Gly Glu 1730 1735 1740 Phe Ile Asp Ala Ser Leu Arg Leu Leu Pro Arg Gly Gly Arg Phe 1745 1750 1755 Ala Glu Met Gly Lys Thr Asp Val Arg Asp Pro Glu Arg Val Ala 1760 1765 1770 Ala Glu Tyr Pro Gly Val Arg Tyr Arg Ala Phe Asp Leu Phe Glu 1775 1780 1785 Ala Asp Leu Asp Arg Leu Arg Glu Ile Leu Arg Glu Leu Leu Ala 1790 1795 1800 Leu Phe Glu Ser Gly Ala Leu Arg Pro Leu Pro Val Arg Ala Trp 1805 1810 1815 Asp Ile Arg Lys Ser Lys Asp Ala Phe Arg His Ile Ala Gln Ala 1820 1825 1830 Arg His Ile Gly Lys Val Ala Leu Thr Met Pro Thr Gly Gly Leu 1835 1840 1845 Gly Asp Gly Val Val Leu Val Thr Gly Gly Thr Gly Gly Leu Gly 1850 1855 1860 Ala Leu Val Ala Arg His Val Val Val Val His Gly Val Arg Arg 1865 1870 1875 Leu Val Leu Val Ser Arg Arg Gly Leu Gly Ala Pro Gly Ala Val 1880 1885 1890 Gly Leu Val Ala Glu Leu Glu Gly Leu Gly Ala Val Val Glu Val 1895 1900 1905 Val Ala Cys Asp Val Ser Asp Arg Val Ala Leu Ala Gly Val Val 1910 1915 1920 Gly Gly Ile Gly Ser Asp Leu Ser Ala Val Val His Thr Ala Gly 1925 1930 1935 Val Val Asp Asp Gly Val Val Gly Ser Leu Ser Val Gly Arg Leu 1940 1945 1950 Ser Ser Val Leu Gly Pro Lys Ala Asp Ala Ala Trp Tyr Leu His 1955 1960 1965 Glu Leu Thr Val Gly Leu Asp Leu Ser Ala Phe Val Leu Phe Ser 1970 1975 1980 Ser Val Ala Gly Val Val Asp Gly Ala Gly Gln Gly Asn Tyr Ala 1985 1990 1995 Ala Ala Asn Val Phe Leu Asp Gly Leu Ala Val Val Arg Arg Gly 2000 2005 2010 Leu Gly Leu Pro Gly Thr Ser Val Ala Trp Gly Leu Trp Glu Gly 2015 2020 2025 Ala Gly Met Gly Ala Val Leu Gly Glu Ala Asp Val Leu Arg Met 2030 2035 2040 Ser Arg Ser Gly Val Leu Gly Leu Ser Val Gly Glu Gly Leu Gly 2045 2050 2055 Leu Phe Asp Val Ala Leu Gly Glu Asp Val Ala Ala Leu Val Pro 2060 2065 2070 Val Arg Leu Asp Leu Gly Ala Leu Arg Ser Arg Val Asp Gly Val 2075 2080 2085 Pro Ala Val Phe Arg Ser Leu Val Arg Val Pro Val Arg Arg Ser 2090 2095 2100 Val Gly Val Gly Val Ser Gly Gly Gly Glu Val Ser Leu Glu Arg 2105 2110 2115 Arg Leu Val Val Leu Asp Ala Gly Glu Arg Glu Arg Val Leu Leu 2120 2125 2130 Glu Leu Val Arg Ser His Val Ala Ala Val Leu Gly Tyr Glu Gly 2135 2140 2145 Ala Gly Ser Ile Glu Pro Gly Arg Ala Phe Ser Asp Ile Gly Phe 2150 2155 2160 Asp Ser Leu Ser Ala Val Glu Leu Arg Asn Arg Leu Asn Gly Glu 2165 2170 2175 Thr Gly Leu Arg Leu Pro Ala Thr Leu Ile Phe Asp Tyr Pro Thr 2180 2185 2190 Pro Gln Ala Leu Ala Glu Tyr Val Ile Val Ala Leu Leu Gly Glu 2195 2200 2205 Glu Ala Ala Asn Ala Pro Ala Leu Pro Pro Thr Glu Ala Pro Thr 2210 2215 2220 Val Thr Gly Thr Asp Asp Asp Pro Val Val Ile Val Gly Met Gly 2225 2230 2235 Cys Arg Phe Pro Gly Asp Val Arg Thr Pro Glu Asp Leu Trp Arg 2240 2245 2250 Leu Val Ser Asn Gly Ser Asp Ala Val Thr Pro Phe Pro Asp Asn 2255 2260 2265 Arg Ala Trp Asp Ile Glu Gly Ile Tyr Asp Pro Leu Pro Gly Val 2270 2275 2280 Ser Gly Lys Thr Tyr Ala Arg Glu Gly Gly Phe Leu His Asp Ala 2285 2290 2295 Ala Glu Phe Asp Pro Glu Phe Phe Gly Ile Ser Pro Arg Glu Ala 2300 2305 2310 Leu Ala Met Asp Pro Gln Gln Arg Leu Leu Leu Glu Thr Ser Trp 2315 2320 2325 Glu Ala Ile Glu Arg Ala Gly Ile Asp Pro Asn Ser Leu Arg Gly 2330 2335 2340 Thr Gln Thr Gly Val Phe Ala Gly Val Met Gln Thr Asp Tyr Gly 2345 2350 2355 Asn Gly Gly Ala Arg Leu Ala Glu Asp Val Glu Gly Tyr Ile Ala 2360 2365 2370 Asn Gly Thr Leu Gly Ser Ile Val Ser Gly Arg Val Ser Tyr Ala 2375 2380 2385 Leu Gly Leu Glu Gly Pro Ala Val Thr Ile Asp Thr Ala Cys Ser 2390 2395 2400 Ser Ser Leu Val Ala Met His Trp Ala Ala His Ala Leu Arg Gln 2405 2410 2415 Gly Glu Cys Ser Leu Ala Leu Ala Gly Gly Val Thr Val Met Ser 2420 2425 2430 Thr Pro Glu Thr Phe Val Asp Phe Ser Leu Gln Arg Gly Leu Ala 2435 2440 2445 Pro Asn Gly Arg Cys Lys Ala Phe Ser Ala Asp Ala Asp Gly Thr 2450 2455 2460 Gly Trp Gly Glu Gly Val Gly Val Leu Val Leu Glu Arg Leu Ser 2465 2470 2475 Asp Ala Arg Arg Asn Gly His Gln Val Leu Ala Val Ile Arg Gly 2480 2485 2490 Ser Ala Leu Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro 2495 2500 2505 Asn Gly Pro Ser Gln Gln Arg Val Ile Arg Gln Ala Leu Val Ser 2510 2515 2520 Ala Gly Leu Thr Thr Ser Asp Val Asp Ala Val Glu Ala His Gly 2525 2530 2535 Thr Gly Thr Thr Leu Gly Asp Pro Ile Glu Ala Gln Ala Leu Leu 2540 2545 2550 Ala Thr Tyr Gly Gln Glu Arg Asp Ala Asp Gln Pro Leu Trp Leu 2555 2560 2565 Gly Ser Val Lys Thr Asn Val Gly His Thr Gln Ala Ala Ala Gly 2570 2575 2580 Val Ala Gly Val Ile Lys Met Val Leu Ala Met Arg Ala Gly Val 2585 2590 2595 Leu Pro Lys Thr Leu His Val Thr Glu Pro Ser Pro His Val Asp 2600 2605 2610 Trp Ser Ala Gly Ala Val Glu Leu Leu Thr Glu Thr Arg Asp Trp 2615 2620 2625 Pro Glu Thr Gly Arg Pro Arg Arg Ala Gly Val Ser Ser Phe Gly 2630 2635 2640 Val Ser Gly Thr Asn Ala His Val Ile Val Glu Gln Ala Pro Ala 2645 2650 2655 Val Glu Glu Glu Pro Thr Arg Ala Leu Pro Ala Leu Pro Val Pro 2660 2665 2670 Trp Ser Ile Ser Ala Lys Ser Ala Asp Ala Leu Arg Gly Gln Ala 2675 2680 2685 Gln Ala Leu Ser Ser Phe Val Ser Ala Ala Gly Asp Val Ser Val 2690 2695 2700 Val Asp Val Ala Tyr Ser Leu Gly Val Ser Arg Ala Gly Leu Glu 2705 2710 2715 His Arg Gly Val Val Val Gly Glu Ser Arg Ala Glu Leu Leu Val 2720 2725 2730 Ala Leu Glu Ser Leu Ala Ser Gly Val Glu Ser Pro Gly Val Val 2735 2740 2745 Thr Gly Arg Val Ala Glu Gly Arg Leu Ala Phe Leu Phe Thr Gly 2750 2755 2760 Gln Gly Ala Gln Arg Val Gly Met Gly Arg Glu Leu Ala Ala Glu 2765 2770 2775 Phe Pro Val Phe Ala Ala Ser Leu Glu Gln Thr Cys Asp Leu Leu 2780 2785 2790 Glu Arg Ala Gly Val Ala Val Arg Glu Val Leu Phe Ala Glu Glu 2795 2800 2805 Gly Ser Ala Glu Ala Ala Leu Leu Thr Arg Thr Val Tyr Ala Gln 2810 2815 2820 Ala Ala Leu Phe Ala Val Glu Val Ala Leu Phe Arg Leu Val Glu 2825 2830 2835 Ser Phe Gly Val Val Pro Asp Phe Val Ala Gly His Ser Val Gly 2840 2845 2850 Glu Ile Ala Ala Ala His Val Ala Gly Val Phe Ser Leu Glu Asp 2855 2860 2865 Ala Val Ser Leu Val Ala Ala Arg Gly Arg Leu Met Asp Ala Leu 2870 2875 2880 Pro Glu Gly Gly Ala Met Val Ala Val Gln Ala Thr Glu Glu Asp 2885 2890 2895 Val Leu Ala Leu Leu Glu Gly Val Glu Asp Ala Ser Ile Ala Ala 2900 2905 2910 Ile Asn Gly Pro Asp Ala Val Val Val Ser Gly Thr Glu Thr Gly 2915 2920 2925 Val Ala Arg Val Val Asp Val Leu Arg Glu Arg Gly Ala Lys Thr 2930 2935 2940 Lys Arg Leu Val Val Ser His Ala Phe His Ser Pro Leu Met Glu 2945 2950 2955 Pro Met Leu Ala Asp Phe Ala Thr Val Val Glu Gly Leu Ser Tyr 2960 2965 2970 Lys Ala Pro Ala Ile Pro Val Val Ser Gly Ser Val Val Gly Ser 2975 2980 2985 Glu Leu Ser Thr Pro Gly Tyr Trp Val Arg His Val Arg Glu Ala 2990 2995 3000 Val Arg Phe Gly Ala Gly Val Glu Thr Leu Leu Gly Ala Gly Val 3005 3010 3015 Ser Ser Phe Leu Glu Ile Gly Pro Asp Gly Val Leu Ser Gly Met 3020 3025 3030 Ala Arg Thr Ser Val Pro Glu Gly Ala Asp Val Glu Cys Ala Pro 3035 3040 3045 Leu Met Arg Arg Asp Arg Ala Glu Val Arg Glu Phe Leu Thr Gly 3050 3055 3060 Leu Ser Arg Leu Ala Val Arg Gly Val Pro Val Ala Trp Glu Ser 3065 3070 3075 Leu Val Glu Gly Gly Arg Arg Val Glu Leu Pro Thr Tyr Ala Phe 3080 3085 3090 Gln Arg Arg Arg Phe Trp Leu Glu Ala Gly Arg Ser Val Thr Asp 3095 3100 3105 Ala Ser Gly Leu Gly Gln Thr Ala Ala Glu His Pro Leu Val Gly 3110 3115 3120 Ala Val Val Gly Leu Ala Gly Gly Asp Gly Val Val Leu Thr Gly 3125 3130 3135 Arg Val Ser Leu His Thr His Pro Trp Leu Ala Asp His Gln Val 3140 3145 3150 Ala Gly Val Thr Leu Leu Pro Gly Thr Gly Phe Val Glu Leu Ala 3155 3160 3165 Val Arg Ala Gly Asp Glu Val Gly Cys Gly Arg Leu Glu Glu Leu 3170 3175 3180 Thr Leu Glu Ala Pro Leu Val Val Pro Asp Arg Gly Ala Val Gln 3185 3190 3195 Leu Gln Val Val Val Gly Ala Leu Glu Thr Ser Gly Val Arg Thr 3200 3205 3210 Val Ser Val Tyr Ser Arg Val Glu Glu Glu Ser Ala Asp Asp Thr 3215 3220 3225 Trp Val Arg His Ala Thr Gly Ala Leu Met Ala Ala Ala Glu Glu 3230 3235 3240 Pro Gly Phe Asp Leu Thr Ala Trp Pro Pro Ala Gly Ala Arg Ala 3245 3250 3255 Val Asp Val Ser Asp Ala Tyr Ala Gly Leu Ala Ser Gln Gly Tyr 3260 3265 3270 Gly Tyr Gly Pro Val Phe Gln Gly Leu Thr Ala Ala Trp Arg Lys 3275 3280 3285 Gly Arg Glu Val Phe Ala Glu Ile Thr Leu Pro Glu Ala Ala Gln 3290 3295 3300 Val Asp Ala Ser Ala Phe Gly Leu His Pro Ala Leu Leu Asp Ala 3305 3310 3315 Ala Leu His Ala Thr Asp Tyr Leu Asp Gln Glu Ser Ala Glu Gly 3320 3325 3330 Thr His Leu Pro Phe Ala Trp Ser Gly Val Ser Leu His Ala Ala 3335 3340 3345 Gly Ala Ser Ala Leu Arg Val Arg Ile Val Ala Thr Gly Lys Asp 3350 3355 3360 Gly Tyr Ala Leu Asp Leu Ala Asp Ser Thr Gly Arg Pro Val Ala 3365 3370 3375 Thr Val Gln Ser Leu Val Thr Arg Pro Val Thr Ala Asp Gln Leu 3380 3385 3390 Ser Glu Ala Ser Ala Thr Gln His Gln Ser Leu Phe Arg Met Glu 3395 3400 3405 Trp Thr Ala Thr Thr Ala Pro Ala Ala Thr Ala Asp Val Arg Trp 3410 3415 3420 Ala Leu Leu Gly Glu Pro Val Ala Glu Leu Gly Asp Leu Ala Gly 3425 3430 3435 Phe Gly Arg Thr Thr Ala Tyr Ala Ser Leu Ala Asp Leu Ala Ala 3440 3445 3450 Ala Asp Ala Asp Thr Val Pro Asp Leu Val Val Leu Pro Leu Gly 3455 3460 3465 Ser Arg Met Ala Glu Gly Ser Asp Val Pro Glu Ala Val Arg Glu 3470 3475 3480 Asn Leu Gly Gln Val Leu Ala Thr Ile Gln Gln Trp Asn Asp Asp 3485 3490 3495 Ser Arg Phe Asp Gly Ser Arg Leu Val Val Leu Thr His Gly Ala 3500 3505 3510 Val Ser Val Ser Asp Asp Glu Ser Leu Thr Ala Leu Asp Leu Ala 3515 3520 3525 Pro Val Trp Gly Leu Val Arg Ser Ala Met Ala Glu Thr Pro Gly 3530 3535 3540 Arg Phe Leu Leu Val Asp Thr Asp Gly Thr Asp Pro Ser Thr Asp 3545 3550 3555 Ala Leu Arg His Leu Ala Glu Leu Gln Glu Ala Glu Phe Ala Leu 3560 3565 3570 Arg Glu Gly Glu Ile Arg Val Pro Arg Leu Ala Arg Val Pro Val 3575 3580 3585 Ala Gly Ala Gly Ala Asp Ile Thr Gly Gly Leu Gly Asp Gly Val 3590 3595 3600 Val Leu Val Thr Gly Gly Thr Gly Gly Leu Gly Ala Val Val Ala 3605 3610 3615 Arg His Ala Val Val Val His Gly Val Arg Arg Leu Val Leu Val 3620 3625 3630 Ser Arg Arg Gly Leu Gly Ala Pro Gly Ala Val Gly Leu Val Ala 3635 3640 3645 Glu Leu Glu Ser Leu Gly Ala Val Val Glu Val Val Ala Cys Asp 3650 3655 3660 Val Ser Asp Arg Val Ala Leu Ala Gly Val Val Gly Gly Ile Gly 3665 3670 3675 Ser Asp Leu Ser Ala Val Val His Thr Ala Gly Val Val Asp Asp 3680 3685 3690 Gly Val Val Gly Ser Leu Ser Val Gly Arg Leu Ser Ser Val Leu 3695 3700 3705 Gly Pro Lys Ala Asp Ala Ala Trp Tyr Leu His Glu Leu Thr Val 3710 3715 3720 Arg Leu Asp Leu Ser Ala Phe Val Leu Phe Ser Ser Val Ala Gly 3725 3730 3735 Val Val Asp Gly Ala Gly Gln Gly Asn Tyr Ala Ala Ala Asn Val 3740 3745 3750 Phe Leu Asp Gly Leu Ala Val Val Arg Arg Gly Leu Gly Leu Pro 3755 3760 3765 Gly Thr Ser Val Ala Trp Gly Leu Trp Glu Gly Ala Gly Met Gly 3770 3775 3780 Ala Val Leu Gly Glu Ala Asp Val Leu Arg Met Ser Arg Ser Gly 3785 3790 3795 Val Leu Gly Leu Ser Val Gly Glu Gly Leu Gly Leu Phe Asp Val 3800 3805 3810 Ala Leu Gly Glu Asp Val Ala Ala Leu Val Pro Val Arg Leu Asp 3815 3820 3825 Leu Gly Ala Leu Arg Ser Arg Val Asp Gly Val Pro Ala Val Phe 3830 3835 3840 Arg Ser Leu Val Arg Val Pro Val Arg Arg Ser Val Gly Val Gly 3845 3850 3855 Val Ser Gly Gly Gly Glu Val Ser Leu Glu Arg Arg Leu Ala Val 3860 3865 3870 Leu Asp Ala Gly Glu Arg Glu Arg Val Leu Leu Glu Leu Val Arg 3875 3880 3885 Ser His Val Ala Ala Val Leu Gly Tyr Glu Gly Ala Gly Ser Ile 3890 3895 3900 Glu Pro Gly Arg Ala Phe Ser Asp Ile Gly Phe Asp Ser Leu Ser 3905 3910 3915 Ala Val Glu Leu Arg Asn Arg Leu Asn Gly Glu Thr Gly Leu Arg 3920 3925 3930 Leu Pro Ala Thr Leu Ile Phe Asp Tyr Pro Thr Pro Gln Ala Leu 3935 3940 3945 Ala Asp Leu Ile Gln Glu Lys Thr Leu Gly Leu Val Asp Ala Ala 3950 3955 3960 Ala Ala Thr Val Ser Thr Thr Val Ser Arg Thr Asp Asp Glu Pro 3965 3970 3975 Ile Ala Ile Val Gly Met Gly Cys Arg Tyr Pro Gly Asp Val Arg 3980 3985 3990 Thr Pro Glu Glu Leu Trp Arg Leu Val Ala Ser Gly Thr Asp Ala 3995 4000 4005 Val Ser Leu Phe Pro Glu Asp Arg Gly Trp Asn Val Asp Ser Ile 4010 4015 4020 Tyr Asp Pro Thr Pro Gly Leu Ser Gly Lys Thr Tyr Thr Arg Glu 4025 4030 4035 Gly Gly Phe Leu His Asp Ala Ala Glu Phe Asp Ala Gly Phe Phe 4040 4045 4050 Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg 4055 4060 4065 Leu Leu Leu Glu Thr Ser Trp Glu Ala Met Glu Arg Ala Gly Ile 4070 4075 4080 Asp Pro Asn Ser Leu Arg Gly Thr Gln Thr Gly Val Phe Ala Gly 4085 4090 4095 Ile Met Tyr His Asp Tyr Gly Ser Arg Val Thr Gln Pro Ser Glu 4100 4105 4110 Glu Val Glu Gly Tyr Leu Gly Asn Gly Ser Ala Gly Ser Ile Ala 4115 4120 4125 Ser Gly Arg Val Ser Tyr Thr Phe Gly Phe Glu Gly Pro Ala Val 4130 4135 4140 Thr Val Asp Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His Trp 4145 4150 4155 Ala Ala Gln Ala Leu Arg Gln Gly Glu Cys Ser Met Ala Leu Ala 4160 4165 4170 Gly Gly Val Thr Val Met Ser Thr Pro Glu Thr Phe Val Asp Phe 4175 4180 4185 Ser Leu Gln Arg Gly Leu Ala Thr Asn Gly Arg Cys Lys Ala Phe 4190 4195 4200 Ser Ser Asp Ala Asp Gly Thr Gly Trp Gly Glu Gly Ala Gly Met 4205 4210 4215 Leu Leu Leu Glu Arg Leu Ser Asp Ala Arg Lys Asn Gly His Glu 4220 4225 4230 Val Leu Ala Val Ile Arg Gly Ser Ala Leu Asn Gln Asp Gly Ala 4235 4240 4245 Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ser Gln Gln Arg Val 4250 4255 4260 Ile Arg Gln Ala Leu Ala Asn Ala Gly Leu Ser Ala Ala Glu Val 4265 4270 4275 Asp Ala Val Glu Ala His Gly Thr Gly Thr Lys Leu Gly Asp Pro 4280 4285 4290 Ile Glu Ala Gln Ala Leu Leu Ala Thr Tyr Gly Gln Glu Arg Asp 4295 4300 4305 Gly Asp Gln Pro Leu Leu Leu Gly Ser Ile Lys Ser Asn Val Gly 4310 4315 4320 His Thr Gln Ala Ala Ala Gly Val Gly Gly Val Ile Lys Met Val 4325 4330 4335 Met Ala Ile Arg Asn Gly Val Leu Pro Lys Thr Leu His Val Thr 4340 4345 4350 Glu Pro Ser Pro His Val Asp Trp Ser Ala Gly Ala Val Glu Leu 4355 4360 4365 Leu Ala Glu Ala Arg Glu Trp Pro Glu Thr Gly Arg Pro Arg Arg 4370 4375 4380 Ala Gly Val Ser Ser Phe Gly Ile Ser Gly Thr Asn Ala His Val 4385 4390 4395 Ile Val Glu Gln Ala Pro Thr Asp Gln Pro Ala Pro Leu Ser Glu 4400 4405 4410 Pro Val Gly Asp Val Pro Gly Leu Pro Val Pro Trp Ile Val Ser 4415 4420 4425 Ala Lys Ser Ala Glu Ala Leu Arg Ala Gln Ala Gly Arg Leu Gly 4430 4435 4440 Ser Phe Leu Gly Glu Thr Gly Val Val Asp Val Pro Ala Val Gly 4445 4450 4455 Trp Ser Leu Val Arg Gly Arg Ser Val Phe Ala His Arg Ala Val 4460 4465 4470 Val Val Gly Gly Glu Trp Asp Glu Leu Leu Ala Gly Val Ala Arg 4475 4480 4485 Val Ala Glu Gly Val Asp Asp Ser Val Val Ser Gly Val Ala Asp 4490 4495 4500 Val Ser Gly Arg Arg Val Phe Val Phe Pro Gly Gln Gly Ser Gln 4505 4510 4515 Trp Val Gly Met Ala Gln Gly Leu Leu Asp Ser Ser Val Val Phe 4520 4525 4530 Thr Glu Arg Met Thr Glu Cys Ala Ala Ala Leu Asp Pro Leu Val 4535 4540 4545 Glu Trp Ser Leu Leu Asp Val Val Arg Gly Val Glu Gly Ala Ala 4550 4555 4560 Ser Leu Glu Arg Val Asp Val Val Gln Pro Val Leu Trp Ala Val 4565 4570 4575 Met Val Ser Leu Ala Ser Val Trp Arg Ser Val Gly Val Val Pro 4580 4585 4590 Asp Ala Val Val Gly His Ser Gln Gly Glu Ile Ala Ala Ala Val 4595 4600 4605 Val Gly Gly Trp Leu Ser Leu Val Asp Gly Ala Arg Val Val Ala 4610 4615 4620 Leu Arg Ser Leu Ala Ile Arg Glu Val Leu Ala Gly Gly Gly Gly 4625 4630 4635 Met Val Ala Val Gln Ala Ala Glu Asp Glu Val Ala Gly Trp Leu 4640 4645 4650 Glu Gly Val Glu Gly Val Gly Ile Ala Ala Val Asn Gly Pro Arg 4655 4660 4665 Ser Val Val Ile Ser Gly Thr Arg Ala Gly Leu Asp Ala Cys Val 4670 4675 4680 Glu Leu Trp Ser Gly Arg Gly Thr Trp Val Lys Arg Val Pro Val 4685 4690 4695 Asp Tyr Ala Ser His Ser Ala Glu Val Glu Arg Val Arg Glu Arg 4700 4705 4710 Val Leu Ala Asp Leu Ala Ser Val Thr Gly Leu Ser Gly Ser Val 4715 4720 4725 Pro Met Leu Ser Thr Met Thr Gly Asp Trp Ile Val Glu Gly Gln 4730 4735 4740 Val Gly Ala Gly Tyr Trp Val Glu Asn Leu Arg Arg Pro Val Leu 4745 4750 4755 Phe Ala Asp Ala Thr Arg Arg Leu Ala Ser Glu Gly Phe Gly Ala 4760 4765 4770 Phe Val Glu Val Ser Ala His Pro Val Leu Val Met Gly Ile Glu 4775 4780 4785 Glu Thr Ile Glu Ala Leu Arg Ser Gly Ala Ala Asp Gly Ala Lys 4790 4795 4800 Ser Gly Ala Gly Glu Glu Ser Ser Ser Ala Val Val Ala Val Gly 4805 4810 4815 Thr Leu Arg Arg Gly Glu Gly Gly Trp Asp Gln Phe Leu Arg Ser 4820 4825 4830 Leu Ala Gly Leu Phe Val Arg Gly Ala Val Ala Pro Asp Trp Glu 4835 4840 4845 Ser Leu Leu Gly Gly Val Arg Pro Arg Val Asp Leu Pro Thr Tyr 4850 4855 4860 Ala Phe Gln Arg Glu Arg Leu Trp Leu Asp Ala Gly Val Val Ala 4865 4870 4875 Gly Asp Val Ser Gly Leu Gly Gln Val Val Val Gly His Pro Leu 4880 4885 4890 Leu Gly Ala Gly Val Gly Val Ala Gly Glu Gly Gly Gly Val Leu 4895 4900 4905 Phe Thr Gly Arg Leu Gly Leu Gly Ser His Pro Trp Leu Gly Asp 4910 4915 4920 His Ala Val Ser Gly Val Val Leu Leu Pro Gly Ala Ala Phe Val 4925 4930 4935 Glu Leu Val Val Arg Ala Gly Asp Glu Val Gly Cys Gly Arg Leu 4940 4945 4950 Glu Glu Leu Thr Leu Ala Ala Pro Leu Val Val Pro Glu Arg Gly 4955 4960 4965 Ser Val Arg Ile Gln Val Val Val Gly Ala Gly Asp Gly Ser Gly 4970 4975 4980 Ala Arg Ser Val Gly Val Trp Ser Ser Val Gly Asp Glu Gly Val 4985 4990 4995 Gly Gly Glu Trp Val Cys His Ala Ser Gly Leu Leu Thr Ala Asp 5000 5005 5010 Val Gly Val Ala Pro Val Leu Gly Gly Val Trp Pro Pro Val Gly 5015 5020 5025 Gly Val Ala Val Asp Val Ser Gly Val Tyr Glu Gly Leu Ala Leu 5030 5035 5040 Glu Gly Tyr Glu Tyr Gly Ser Val Phe Arg Gly Leu Arg Ser Val 5045 5050 5055 Trp Arg Arg Gly Asp Glu Val Phe Ala Glu Val Ala Leu Gly Glu 5060 5065 5070 Gly Val Gly Val Glu Gly Phe Gly Leu His Pro Ala Leu Leu Asp 5075 5080 5085 Ala Ala Leu Gln Ala Ala Gly Phe Gly Ser Phe Val Pro Glu Ser 5090 5095 5100 Glu Ala Gly Ser Glu Ala Gly Ser Gly Gly Val Arg Leu Pro Phe 5105 5110 5115 Ser Trp Ser Gly Val Ser Leu Phe Ala Ser Gly Ala Ser Val Gly 5120 5125 5130 Arg Val Arg Leu Trp Pro Val Gly Gly Asp Gly Phe Gly Val Glu 5135 5140 5145 Leu Phe Asp Gly Val Gly Met Pro Val Ala Arg Val Asp Ala Leu 5150 5155 5160 Val Thr Arg Glu Ile Ser Ala Gly Gln Leu Gly Ala Ala Ala Gly 5165 5170 5175 Ala Gly Ser Leu Val Gly Gly Glu Ser Leu Phe Arg Val Glu Trp 5180 5185 5190 Ala Pro Val Ser Gly Val Ala Pro Ala Ser Ala Gly Val Gly Gly 5195 5200 5205 Cys Val Val Val Gly Ala Gly Ser Val Leu Ser Gly Phe Gly Glu 5210 5215 5220 Val Val Pro Asp Leu Ala Ala Val Ser Ala Gly Ser Ala Asp Gly 5225 5230 5235 Val Gly Val Pro Gly Trp Val Leu Val Asp Val Asp Ala Trp Leu 5240 5245 5250 Gly Ala Asp Leu Ala Val Gly Val Val Ser Gly Glu Gly Val Pro 5255 5260 5265 Val Val Ala Arg Gly Val Val Ala Arg Val Leu Gly Leu Val Arg 5270 5275 5280 Glu Trp Leu Gly Asp Glu Arg Trp Val Ser Ser Arg Leu Val Trp 5285 5290 5295 Val Thr Arg Gly Ala Val Gly Ala Arg Val Leu Asp Glu Val Ser 5300 5305 5310 Gly Val Val Ser Ser Gly Leu Trp Gly Leu Val Arg Ala Ala Gln 5315 5320 5325 Ser Glu His Pro Asp Arg Phe Ala Leu Leu Asp Leu Asp Ser Ala 5330 5335 5340 Thr Ala Val Asp Ala Val Arg Asp Gly Val Leu Gly Leu Leu Ala 5345 5350 5355 Ala Gly Glu Pro Gln Leu Val Val Arg Glu Gly Glu Val Leu Ala 5360 5365 5370 Ala Arg Leu Thr Pro Ala His Thr Thr Asp Glu Pro Thr Gly Gln 5375 5380 5385 Glu Phe Gly Lys Ala Ala Thr Gly Thr Val Leu Val Thr Gly Gly 5390 5395 5400 Thr Gly Gly Leu Gly Ala Val Val Ala Arg His Leu Val Thr Glu 5405 5410 5415 His Gly Ala Gln Arg Leu Leu Leu Thr Ser Arg Arg Gly Ile Asn 5420 5425 5430 Ala Pro Gly Ala Ala Glu Leu Val Ala Glu Leu Ala Glu Leu Gly 5435 5440 5445 Ala Arg Ala Asp Val Ala Ala Cys Asp Val Ser Asp Arg Ala Ala 5450 5455 5460 Leu Lys Glu Leu Leu Ala Gly Val Pro Gly Asp Ala Pro Leu Thr 5465 5470 5475 Ala Val Val His Ala Ala Gly Val Leu Asp Asp Gly Val Ile Glu 5480 5485 5490 Ser Met Thr Ala Asp Arg Leu Asp Ala Val Met Arg Pro Lys Val 5495 5500 5505 Asp Ala Ala Trp His Leu His Glu Leu Thr Ala Asp Arg Glu Leu 5510 5515 5520 Asp Ala Phe Val Leu Phe Ser Ser Ala Ala Gly Thr Leu Asp Gly 5525 5530 5535 Ala Gly Gln Ser Asn Tyr Ala Ala Ala Asn Val Phe Leu Asp Ala 5540 5545 5550 Leu Ala Gln Tyr Arg Arg Gly Gln Gly Leu Ala Gly Leu Ser Leu 5555 5560 5565 Ala Trp Gly Leu Trp Gly Glu Ser Thr Gly Met Val Gly Ala Leu 5570 5575 5580 Glu Gly Ser Asp Leu Asp Arg Ile Gly Arg Ser Gly Val Arg Ala 5585 5590 5595 Leu Ser Ser Ala Glu Gly Leu Ala Leu Phe Asp Ala Ala Ala Val 5600 5605 5610 Leu Gly Glu Pro Ala Val Leu Pro Val Ala Leu Asp Leu Gly Val 5615 5620 5625 Leu Arg Thr Gln Pro Arg Asn Gln Val Pro Ala Ile Leu Arg Gly 5630 5635 5640 Phe Ala Ala Gly Pro Thr Arg Arg Thr Ala Val Thr Gly Gly Pro 5645 5650 5655 Glu Thr Asp Gln Glu Ala Leu Thr Arg Arg Leu Ala Ser Leu Ser 5660 5665 5670 Pro Ala Asp Arg Asp Arg Phe Leu Leu Asp Leu Val Arg Thr Gln 5675 5680 5685 Val Ala Gly Val Leu Gly Tyr Ser Gly Pro Asp Ala Ile Asp Pro 5690 5695 5700 Gln Arg Gly Phe Gln Glu Leu Gly Val Asp Ser Leu Ala Ala Val 5705 5710 5715 Gln Ile Arg Asn Arg Leu Gly Ala Ala Thr Gly Val Arg Pro Pro 5720 5725 5730 Thr Thr Leu Val Phe Asp Tyr Pro Thr Pro Asp Ala Val Ala Gly 5735 5740 5745 Tyr Phe Lys Glu His Leu Val Ile Glu Glu Glu Asp Ser Thr Ala 5750 5755 5760 Glu Leu Met Arg Glu Ile Ala Arg Leu Glu Ala Ala Val Thr Ser 5765 5770 5775 Ala Ala Ser Ser Ala Gly Gly Ala Gly Leu Ala Pro Ala Val Asp 5780 5785 5790 Arg Leu Arg Ala Met Ala Ala Lys Leu Ala Asp Ala Asp Ala Gln 5795 5800 5805 Arg Ala Asp Glu Asp Asp Pro Gly Leu Glu Ser Ala Thr Ala Asp 5810 5815 5820 Glu Leu Phe Asp Ile Leu Asp Gly Glu Leu Ser Thr Asp 5825 5830 5835 21 23 DNA Artificial Sequence Primer for PCR (46DH-1) 21 acsggycsbg ccgchttcat cgg 23 22 24 DNA Artificial Sequence Primer for PCR (46DH-2) 22 grwrctgrtr sggccgtagt tgtt 24 23 22 DNA Artificial Sequence Primer for PCR (23DH-1) 23 aggccacccg sagcaactac ac 22 24 21 DNA Artificial Sequence Primer for PCR (23DH-2) 24 gaascgsccg ccctcctcsg a 21 25 26 DNA Artificial Sequence Primer for PCR (vinC-Nterm) 25 aaggtaccat atgcgcgtcc tgatga 26 26 26 DNA Artificial Sequence Primer for PCR (vinC-Cterm) 26 cccggatccg ctgggcggag tgctac 26 

What is claimed is:
 1. A gene cluster comprising a base sequence represented by base Nos. 1-64492 shown in the SEQ ID No. 1 in the sequence listing.
 2. A polypeptide comprising an amino acid sequence of the following (a) or (b): (a) a polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-419 shown in the SEQ ID No. 4 in the sequence listing, (b) a polypeptide comprising an amino acid sequence having at least 90% homology with the amino acid sequence (a), and exhibiting enzymatic activity as a glycosyltransferase.
 3. A gene encoding a polypeptide according to claim
 2. 4. A gene comprising a base sequence the following (c), (d) or (e): (c) a gene comprising a base sequence represented by base Nos. 2790-4049 shown in the SEQ ID No. 1 in the sequence listing, (d) a gene comprising a base sequence having at least 90% homology with the base sequence (c), and encoding a polypeptide exhibiting enzymatic activity as a glycosyltransferase, (e) a gene comprising a base sequence that hybridizes with the base sequence (c) under a stringent condition, and encoding a polypeptide exhibiting enzymatic activity as a glycosyltransferase.
 5. A polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-355 shown in the SEQ ID No. 2 in the sequence listing.
 6. A polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-323 shown in the SEQ ID No. 3 in the sequence listing.
 7. A polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-2260 shown in the SEQ ID No. 5 in the sequence listing.
 8. A polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-3362 shown in the SEQ ID No. 6 in the sequence listing.
 9. A polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-3808 shown in the SEQ ID No. 7 in the sequence listing.
 10. A polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-236 shown in the SEQ ID No. 8 in the sequence listing.
 11. A polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-397 shown in the SEQ ID No. 9 in the sequence listing.
 12. A polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-493 shown in the SEQ ID No. 10 in the sequence listing.
 13. A polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-330 shown in the SEQ ID No. 11 in the sequence listing.
 14. A polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-158 shown in the SEQ ID No. 12 in the sequence listing.
 15. A polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-469 shown in the SEQ ID No. 13 in the sequence listing.
 16. A polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-299 shown in the SEQ ID No. 14 in the sequence listing.
 17. A polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-327 shown in the SEQ ID No. 15 in the sequence listing.
 18. A polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-82 shown in the SEQ ID No. 16 in the sequence listing.
 19. A polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-524 shown in the SEQ ID No. 17 in the sequence listing.
 20. A polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-478 shown in the SEQ ID No. 18 in the sequence listing.
 21. A polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-414 shown in the SEQ ID No. 19 in the sequence listing.
 22. A polypeptide comprising an amino acid sequence represented by amino acid Nos. 1-5836 shown in the SEQ ID No. 20 in the sequence listing.
 23. A method for production of vicenistatin by catalytic reaction of the glycosyltransferase comprising the polypeptide according to claim 2, using dTDP-vicenisamine as a starting material. 